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Endothelial adherens junctions and
Endothelial adherens junctions and the actin cytoskeleton: an 'infinity net'?
Abstract
A recent paper in BMC Biology reports that actin stress fibers in adjacent cultured endothelial cells are linked through adherens junctions. This organization might provide a super-cellular network that could enable coordinated signaling and structural responses in endothelia.
See research article http://www.biomedcentral.com/1741-7007/8/11 webcite
Minireview
The title of this minireview is inspired by the work of the Japanese artist Yayoi Kusama, who paints wonderful networks as one of her favorite subjects. As an artist, she can evoke images and concepts that are sometimes beyond her own knowledge: in this case her idea of a continuous network well suits a model of intercellular cytoskeletal linking suggested by a recent paper published in BMC Biology by Millan et al. [1]. Working with cultured human umbilical cord vein endothelial cells they find that actin-based stress fibers in adjacent endothelial cells in confluent culture can become linked through adherens junctions. This organization could, in theory, enable a communication network extending throughout the endothelium, as well as maintaining structural coherence and increasing resistance to stress. This capacity could be crucial to the function and adaptability of the endothelium, which is continuously exposed to changes in blood flow, whether in normal physiologic situations, or during inflammation or angiogenesis.
This is a novel extension of a concept first used for epithelial sheets [2] to endothelial monolayers.
The adherens junction
The intercellular junctions between endothelial cells maintain endothelial integrity, controlling the movement of solutes between bloodstream and tissues, and the flow of white blood cells between blood and tissues, especially at sites of infection and inflammation. Adherens junctions both mediate adhesion between cells and support the local concentration of scaffolding and signaling molecules. This enables molecular interactions that otherwise would not take place and the segregation of signaling molecules for specific regulation (for a general description of the organization of cell-cell contacts in endothelial cells see [3]). Adherens junctions are based on the transmembrane adhesive receptor that belongs to the cadherin family and a notable and specific feature of the endothelial junctions is the presence of the tissue-specific vascular endothelial (VE)-cadherin. VE-cadherin is constitutively linked through its cytoplasmic tail directly to β- or γ-catenin (plakoglobin) or the catenin p120, and indirectly to α-catenin via β- or γ-catenin.
From studies in epithelial and endothelial cells, the conventional view of adherens junctions is that they link through the catenin complex to cortical actin filaments that lie parallel to the cell surface. In their confluent endothelial cell cultures, however, Millan et al. [1] found an additional type of adherens junction organization. They found that staining for junctional components such as VE-cadherin revealed lines of staining running in from the cell surface rather than lying parallel to the cell surface as in conventional adherens junction complexes. The authors call these novel junctions 'discontinuous adherens junctions' to distinguish them from those more familiar from epithelial cells. Further staining for VE-cadherin and actin revealed that actin stress fibers running perpendicular to the cell surface were associated with these discontinuous adherens junctions (Figure 1).
Figure 1. Structural and functional actin filament organization at cell-cell junctions in endothelial cells. In quiescent cells, junctional actin filaments can be oriented either parallel (left-hand image) or perpendicular (center image) to the cell surface. A question mark indicates that it is not known whether these two types of arrangement can interchange, or whether the perpendicular arrangement must arise de novo. Actomyosin stress fibers are anchored to the membrane through adherens junctions[1]. VE-cadherin is required, but the stress fibers are not directly linked to the cadherin-catenin complex. They are possibly tethered to adherens junctions by afadin or other, still unidentified molecules (see Figure 2, and text for details). Subdomains with perpendicular actin fibers, called 'discontinuous adherens junctions' in [1], are dynamic, and undergo constant reorganization. In these areas, actin fibers of adjoining cells are connected through adherens junctions into a supercellular network [1]. In quiescent endothelial cells, actin stress fibers are polymerized through the action of Rac and Rho, Rho signaling through the actin nucleator Dia (diaphanous-related formin) [7]. Various stimuli activate the endothelium and induce actomyosin contraction at the dynamic domains (right-hand image), with Rho signaling through the protein kinase ROCK [7], and resulting in the opening of intercellular gaps, making the endothelium permeable to fluid and molecules, and facilitating the transmigration of leukocytes. In activated conditions, adherens junctions are also functionally and structurally modified (indicated by the change of the junctional symbol to blue). The molecular details of such alterations are still incompletely understood. The association of actin with adherens junctions is also likely to be modified. It remains to be defined at which molecules/structures (indicated by question marks) anchor the actin fibers at the ends that are not interacting with the adherens junction. This anchoring is critical to allow productive contraction.
Local regulation of actin by adherens junctions in endothelial cells
At early phases of junction formation, actin filaments organize perpendicularly to the membrane through the local accumulation of actin-nucleating complexes [4]. Further stages of junction maturation are accompanied by the development of actin fibers parallel to the membrane to form a peripheral actin rim ([5] and references therein). It is not clear at present whether the perpendicular actin fibers described by Millan et al. [1] are residual early fibers or derive by de novo organization. Actin reorganization at cell-cell junctions proceeds through the action of several regulators that concentrate locally (Figure 2).
Figure 2. Schematic representation of some signaling networks that control the formation of actin stress fibers at adherens junctions in endothelial cells. VE-cadherin can directly or indirectly recruit regulators of actin polymerization, among which is the small GTPase Rac as well as regulators of Rac and Rho. Regulators include Rac activators, such as the small GPTPase Rap1 (linked through CCM1 and β-catenin) and its guanine-exchange factor, PDZ-GEF (linked through MAGI and β-catenin), the Rac guanine-exchange factor Tiam (through the local activation of phosphoinositide 3-kinase (PI3K), and Vav2. Tiam and Rac can be localized at junctions also through the Par polarity complex (not shown in the figure) [17]. Rho inhibitors include CCM2 (linked through CCM1 and β-catenin and down-regulating Rho activity through a still poorly defined mechanism) and p190RhoGAP (linked through p120). Rap1 can convey signals from cAMP, through its GEF, Epac [8]. Therefore, local clustering of VE-cadherin as well as regulation of the association of β-catenin and p120 to VE-cadherin appears crucial to the assembly of a molecular unit controlling actin polymerization and contraction at junctions. Pharmacological tools to modulate this complex might be of therapeutic relevance.
A crucial molecule in the organization of actin at the adherens junctions is α-catenin. The molecular features of the relationship between α-catenin and actin have been profoundly revised in recent years (reviewed in [6]). Instead of a 'simple' bridge between junctional cadherin and the actin microfilament cytoskeleton, α-catenin is now considered to act as a regulator of actin polymerization. For allosteric reasons α-catenin cannot bind at the same time to β-catenin and actin filaments. Dimeric α-catenin binds with high affinity to actin filaments, and inhibiting Arp2/3 activity suppresses actin branching. In addition, dimeric α-catenin promotes the formation of linear actin cables by activating formin (Figure 2; [6] and references therein).
If α-catenin is not the tether between VE-cadherin and actin, which junctional components might be? This is not known at present. Afadin, a cytoplasmic molecule localized at adherens junctions bound to the nectin adhesive receptors, can anchor actin to the plasma membrane and could contribute to the stabilization of the peripheral actin rim [5,6]. Which other junctional components might tether actin filaments to adherens junctions remains to be determined.
In addition, β-catenin has an important role in regulating the behavior of actin. Small GTPases of the Rho family that have crucial effects on the control of actin polymerization [4] and on the contractility of actomyosin are recruited and regulated at adherens junctions through β-catenin (Figure 2; see [7] for a comprehensive review of the roles of these GTPases in epithelial cells).
Remodeling or de novo polymerization of actin filaments can be controlled by the GTPases Rac and Rho, while Rho also affects the contractility of actomyosin, the complex of actin and myosin that makes up the contractile stress fibers. Rac signaling at adherens junctions is likely to be downstream of the small GTPase Rap1 [8], which in endothelial cells can be localized at adherens junctions in a complex with VE-cadherin through CCM1 and β-catenin [9]. In addition, Rap1 can be activated at junctions by PDZ-GEF, recruited locally by the protein MAGI, which is linked to VE-cadherin through β-catenin [10]. Rap1 can also convey signals from cAMP, through its guanine nucleotide exchange factor (GEF) Epac, to stabilize the barrier properties of the endothe
Abstract
A recent paper in BMC Biology reports that actin stress fibers in adjacent cultured endothelial cells are linked through adherens junctions. This organization might provide a super-cellular network that could enable coordinated signaling and structural responses in endothelia.
See research article http://www.biomedcentral.com/1741-7007/8/11 webcite
Minireview
The title of this minireview is inspired by the work of the Japanese artist Yayoi Kusama, who paints wonderful networks as one of her favorite subjects. As an artist, she can evoke images and concepts that are sometimes beyond her own knowledge: in this case her idea of a continuous network well suits a model of intercellular cytoskeletal linking suggested by a recent paper published in BMC Biology by Millan et al. [1]. Working with cultured human umbilical cord vein endothelial cells they find that actin-based stress fibers in adjacent endothelial cells in confluent culture can become linked through adherens junctions. This organization could, in theory, enable a communication network extending throughout the endothelium, as well as maintaining structural coherence and increasing resistance to stress. This capacity could be crucial to the function and adaptability of the endothelium, which is continuously exposed to changes in blood flow, whether in normal physiologic situations, or during inflammation or angiogenesis.
This is a novel extension of a concept first used for epithelial sheets [2] to endothelial monolayers.
The adherens junction
The intercellular junctions between endothelial cells maintain endothelial integrity, controlling the movement of solutes between bloodstream and tissues, and the flow of white blood cells between blood and tissues, especially at sites of infection and inflammation. Adherens junctions both mediate adhesion between cells and support the local concentration of scaffolding and signaling molecules. This enables molecular interactions that otherwise would not take place and the segregation of signaling molecules for specific regulation (for a general description of the organization of cell-cell contacts in endothelial cells see [3]). Adherens junctions are based on the transmembrane adhesive receptor that belongs to the cadherin family and a notable and specific feature of the endothelial junctions is the presence of the tissue-specific vascular endothelial (VE)-cadherin. VE-cadherin is constitutively linked through its cytoplasmic tail directly to β- or γ-catenin (plakoglobin) or the catenin p120, and indirectly to α-catenin via β- or γ-catenin.
From studies in epithelial and endothelial cells, the conventional view of adherens junctions is that they link through the catenin complex to cortical actin filaments that lie parallel to the cell surface. In their confluent endothelial cell cultures, however, Millan et al. [1] found an additional type of adherens junction organization. They found that staining for junctional components such as VE-cadherin revealed lines of staining running in from the cell surface rather than lying parallel to the cell surface as in conventional adherens junction complexes. The authors call these novel junctions 'discontinuous adherens junctions' to distinguish them from those more familiar from epithelial cells. Further staining for VE-cadherin and actin revealed that actin stress fibers running perpendicular to the cell surface were associated with these discontinuous adherens junctions (Figure 1).
Figure 1. Structural and functional actin filament organization at cell-cell junctions in endothelial cells. In quiescent cells, junctional actin filaments can be oriented either parallel (left-hand image) or perpendicular (center image) to the cell surface. A question mark indicates that it is not known whether these two types of arrangement can interchange, or whether the perpendicular arrangement must arise de novo. Actomyosin stress fibers are anchored to the membrane through adherens junctions[1]. VE-cadherin is required, but the stress fibers are not directly linked to the cadherin-catenin complex. They are possibly tethered to adherens junctions by afadin or other, still unidentified molecules (see Figure 2, and text for details). Subdomains with perpendicular actin fibers, called 'discontinuous adherens junctions' in [1], are dynamic, and undergo constant reorganization. In these areas, actin fibers of adjoining cells are connected through adherens junctions into a supercellular network [1]. In quiescent endothelial cells, actin stress fibers are polymerized through the action of Rac and Rho, Rho signaling through the actin nucleator Dia (diaphanous-related formin) [7]. Various stimuli activate the endothelium and induce actomyosin contraction at the dynamic domains (right-hand image), with Rho signaling through the protein kinase ROCK [7], and resulting in the opening of intercellular gaps, making the endothelium permeable to fluid and molecules, and facilitating the transmigration of leukocytes. In activated conditions, adherens junctions are also functionally and structurally modified (indicated by the change of the junctional symbol to blue). The molecular details of such alterations are still incompletely understood. The association of actin with adherens junctions is also likely to be modified. It remains to be defined at which molecules/structures (indicated by question marks) anchor the actin fibers at the ends that are not interacting with the adherens junction. This anchoring is critical to allow productive contraction.
Local regulation of actin by adherens junctions in endothelial cells
At early phases of junction formation, actin filaments organize perpendicularly to the membrane through the local accumulation of actin-nucleating complexes [4]. Further stages of junction maturation are accompanied by the development of actin fibers parallel to the membrane to form a peripheral actin rim ([5] and references therein). It is not clear at present whether the perpendicular actin fibers described by Millan et al. [1] are residual early fibers or derive by de novo organization. Actin reorganization at cell-cell junctions proceeds through the action of several regulators that concentrate locally (Figure 2).
Figure 2. Schematic representation of some signaling networks that control the formation of actin stress fibers at adherens junctions in endothelial cells. VE-cadherin can directly or indirectly recruit regulators of actin polymerization, among which is the small GTPase Rac as well as regulators of Rac and Rho. Regulators include Rac activators, such as the small GPTPase Rap1 (linked through CCM1 and β-catenin) and its guanine-exchange factor, PDZ-GEF (linked through MAGI and β-catenin), the Rac guanine-exchange factor Tiam (through the local activation of phosphoinositide 3-kinase (PI3K), and Vav2. Tiam and Rac can be localized at junctions also through the Par polarity complex (not shown in the figure) [17]. Rho inhibitors include CCM2 (linked through CCM1 and β-catenin and down-regulating Rho activity through a still poorly defined mechanism) and p190RhoGAP (linked through p120). Rap1 can convey signals from cAMP, through its GEF, Epac [8]. Therefore, local clustering of VE-cadherin as well as regulation of the association of β-catenin and p120 to VE-cadherin appears crucial to the assembly of a molecular unit controlling actin polymerization and contraction at junctions. Pharmacological tools to modulate this complex might be of therapeutic relevance.
A crucial molecule in the organization of actin at the adherens junctions is α-catenin. The molecular features of the relationship between α-catenin and actin have been profoundly revised in recent years (reviewed in [6]). Instead of a 'simple' bridge between junctional cadherin and the actin microfilament cytoskeleton, α-catenin is now considered to act as a regulator of actin polymerization. For allosteric reasons α-catenin cannot bind at the same time to β-catenin and actin filaments. Dimeric α-catenin binds with high affinity to actin filaments, and inhibiting Arp2/3 activity suppresses actin branching. In addition, dimeric α-catenin promotes the formation of linear actin cables by activating formin (Figure 2; [6] and references therein).
If α-catenin is not the tether between VE-cadherin and actin, which junctional components might be? This is not known at present. Afadin, a cytoplasmic molecule localized at adherens junctions bound to the nectin adhesive receptors, can anchor actin to the plasma membrane and could contribute to the stabilization of the peripheral actin rim [5,6]. Which other junctional components might tether actin filaments to adherens junctions remains to be determined.
In addition, β-catenin has an important role in regulating the behavior of actin. Small GTPases of the Rho family that have crucial effects on the control of actin polymerization [4] and on the contractility of actomyosin are recruited and regulated at adherens junctions through β-catenin (Figure 2; see [7] for a comprehensive review of the roles of these GTPases in epithelial cells).
Remodeling or de novo polymerization of actin filaments can be controlled by the GTPases Rac and Rho, while Rho also affects the contractility of actomyosin, the complex of actin and myosin that makes up the contractile stress fibers. Rac signaling at adherens junctions is likely to be downstream of the small GTPase Rap1 [8], which in endothelial cells can be localized at adherens junctions in a complex with VE-cadherin through CCM1 and β-catenin [9]. In addition, Rap1 can be activated at junctions by PDZ-GEF, recruited locally by the protein MAGI, which is linked to VE-cadherin through β-catenin [10]. Rap1 can also convey signals from cAMP, through its guanine nucleotide exchange factor (GEF) Epac, to stabilize the barrier properties of the endothe
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Junctions adherens บุผนังหลอดเลือดและ cytoskeleton แอกติน: มี 'อินฟินิตี้สุทธิ'บทคัดย่อรายงานล่าสุดทางชีววิทยา BMC รายงานว่า เส้นใยความเครียดแอกตินในเซลล์บุผนังหลอดเลือดติดอ่างเชื่อมโยงผ่าน adherens junctions องค์กรนี้อาจมีเครือข่ายเซลลูลาร์เตอร์รุ่นที่สามารถเปิดใช้งานตามปกติประสานและโครงสร้างการตอบสนองใน endotheliaดูงานวิจัยบทความ http://www.biomedcentral.com/1741-7007/8/11 webciteMinireviewชื่อของ minireview นี้เป็นแรงบันดาลใจ โดยการทำงานของศิลปินญี่ปุ่น Kusama ยะโยะอิผู้วาดเครือข่ายยอดเยี่ยมเป็นหนึ่งในเรื่องโปรดของเธอ เป็นศิลปิน เธอสามารถเรามอบให้ภาพและแนวคิดที่บางครั้งอยู่นอกเหนือความรู้ของตนเอง: ในกรณีนี้ ความคิดของเครือข่ายอย่างต่อเนื่องดีเหมาะสมกับรุ่นของ intercellular cytoskeletal เชื่อมโยงแนะนำกระดาษล่าสุดที่เผยแพร่ในชีววิทยา BMC โดย Millan et al. [1] พวกเขาทำงานกับเซลล์บุผนังหลอดเลือดหลอดเลือดดำสายสะดืออ่างมนุษย์พบว่า เส้นใยแอกตินตามความเครียดในเซลล์บุผนังหลอดเลือดติดในวัฒนธรรม confluent สามารถกลายเป็นลิงค์ผ่าน adherens junctions องค์กรนี้สามารถ ทฤษฎี เปิดการใช้งานเครือข่ายสื่อสารขยายทั่ว endothelium รวมทั้งรักษาโครงสร้างศักยภาพ และเพิ่มความต้านทานต่อความเครียด กำลังการผลิตนี้อาจจะสำคัญกับฟังก์ชันและหลากหลายของ endothelium ซึ่งเป็นอย่างต่อเนื่องสัมผัสการเปลี่ยนแปลงในกระแสเลือด ในสถานการณ์ปกติ physiologic หรือ ระหว่างการอักเสบหรือการ angiogenesisนี้มีส่วนขยายเป็นนวนิยายของแนวคิดแรก ใช้แผ่น epithelial [2] การ monolayers บุผนังหลอดเลือดเชื่อมต่อ adherensJunctions intercellular ระหว่างเซลล์บุผนังหลอดเลือดรักษาความสมบูรณ์ของบุผนังหลอดเลือด การควบคุมการเคลื่อนไหวของ solutes ระหว่างกระแสเลือด และเนื้อเยื่อ และการไหลเวียนของเซลล์เม็ดเลือดขาวระหว่างเลือดและเนื้อเยื่อ โดยเฉพาะอย่างยิ่งที่เว็บไซต์ของการติดเชื้อและอักเสบ Adherens junctions ทั้งสื่อกลางยึดเกาะระหว่างเซลล์ และสนับสนุนความเข้มข้นภายในของนั่งร้าน และสัญญาณโมเลกุล ทำให้โต้ตอบระดับโมเลกุลที่มิฉะนั้น จะไม่มีสถานที่และการแบ่งแยกสัญญาณโมเลกุลสำหรับระเบียบเฉพาะ (สำหรับคำอธิบายทั่วไปขององค์กรที่ติดต่อเซลล์เซลล์ในเซลล์บุผนังหลอดเลือดดู [3]) Adherens junctions ยึดตัวรับกาว transmembrane สมาชิกครอบครัว cadherin และคุณลักษณะเฉพาะ และโดดเด่นของ junctions บุผนังหลอดเลือดจะอยู่ในเฉพาะเนื้อเยื่อหลอดเลือดบุผนังหลอดเลือด (VE) -cadherin Constitutively สัมพันธ์ VE cadherin ผ่าน cytoplasmic หางตรงβ - หรือγ-catenin (plakoglobin) หรือ catenin p120 และอ้อมα-catenin ผ่านβ - หรือγ-cateninจากการศึกษาในเซลล์บุผนังหลอดเลือด และ epithelial มุมมองปกติของ adherens junctions เป็นว่า พวกเขาเชื่อมโยงผ่าน catenin ซับซ้อน filaments แอกตินเนื้อแน่นที่นอนขนานกับพื้นผิวเซลล์ ในวัฒนธรรมของเซลล์บุผนังหลอดเลือด confluent ไร Millan et al. [1] พบชนิดเพิ่มเติมเป็น adherens เชื่อมต่อองค์กร พวกเขาพบว่า การย้อมสีสำหรับคอมโพเนนต์ junctional เช่น VE cadherin เปิดเผยบรรทัดของการย้อมสีใช้ในจากพื้นผิวของเซลล์ แทนที่ขนานกับผิวเซลล์ในคอมเพล็กซ์แยก adherens ธรรมดา ผู้เขียนเรียก junctions นวนิยายเหล่านี้ 'adherens ไม่ต่อเนื่อง junctions' จะแตกต่างจากที่คุ้นเคยจาก epithelial เซลล์ การย้อมสีเพิ่มเติมสำหรับ VE cadherin และแอกตินเปิดเผยว่า แอกตินเส้นใยความเครียดทำงานตั้งฉากกับพื้นผิวของเซลล์เกี่ยวข้องกับ junctions เหล่านี้ adherens ไม่ต่อเนื่อง (รูปที่ 1) Figure 1. Structural and functional actin filament organization at cell-cell junctions in endothelial cells. In quiescent cells, junctional actin filaments can be oriented either parallel (left-hand image) or perpendicular (center image) to the cell surface. A question mark indicates that it is not known whether these two types of arrangement can interchange, or whether the perpendicular arrangement must arise de novo. Actomyosin stress fibers are anchored to the membrane through adherens junctions[1]. VE-cadherin is required, but the stress fibers are not directly linked to the cadherin-catenin complex. They are possibly tethered to adherens junctions by afadin or other, still unidentified molecules (see Figure 2, and text for details). Subdomains with perpendicular actin fibers, called 'discontinuous adherens junctions' in [1], are dynamic, and undergo constant reorganization. In these areas, actin fibers of adjoining cells are connected through adherens junctions into a supercellular network [1]. In quiescent endothelial cells, actin stress fibers are polymerized through the action of Rac and Rho, Rho signaling through the actin nucleator Dia (diaphanous-related formin) [7]. Various stimuli activate the endothelium and induce actomyosin contraction at the dynamic domains (right-hand image), with Rho signaling through the protein kinase ROCK [7], and resulting in the opening of intercellular gaps, making the endothelium permeable to fluid and molecules, and facilitating the transmigration of leukocytes. In activated conditions, adherens junctions are also functionally and structurally modified (indicated by the change of the junctional symbol to blue). The molecular details of such alterations are still incompletely understood. The association of actin with adherens junctions is also likely to be modified. It remains to be defined at which molecules/structures (indicated by question marks) anchor the actin fibers at the ends that are not interacting with the adherens junction. This anchoring is critical to allow productive contraction.ระเบียบภายในของแอกตินโดย adherens junctions ในเซลล์บุผนังหลอดเลือดในระยะแรก ๆ ของการก่อตัวทาง แอกติน filaments จัด perpendicularly เพื่อเยื่อผ่านสะสมเฉพาะของแอกติน nucleating คอมเพล็กซ์ [4] ขั้นตอนต่อไปของพ่อแม่แยกเพิ่มเติม โดยการพัฒนาเส้นใยแอกตินขนานกับเมมเบรนแบบริมต่อพ่วงแอกติน ([5] และอ้างอิง therein) มันไม่ได้ชัดเจนในปัจจุบันว่าเส้นใยแอกตินตั้งฉากอธิบายโดย Millan et al. [1] เหลือเส้นใยต้น หรือได้รับ de novo องค์กร แอกตินมากที่เซลล์เซลล์ junctions ดำเนินผ่านการดำเนินการของหน่วยงานกำกับดูแลต่าง ๆ ที่ตั้งภายใน (รูปที่ 2) รูปที่ 2 แสดงแผนผังวงจรของบางเครือข่าย signaling ที่ควบคุมการก่อตัวของแอกตินเส้นใยความเครียดที่ junctions adherens ในเซลล์บุผนังหลอดเลือด VE cadherin สามารถโดยตรง หรือโดยอ้อมรับสมัครเร็คกูเลเตอร์ของแอกติน polymerization ระหว่างความหมายเล็ก GTPase Rac เร็คกูเลเตอร์ของ Rac และครอ เร็คกูเลเตอร์รวม Rac คริปต์ GPTPase Rap1 เล็กที่ (เชื่อมโยงผ่าน CCM1 และβ-catenin) และปัจจัยของ guanine-แลกเปลี่ยน PDZ GEF (เชื่อมโยงผ่านโหราจารย์และβ-catenin), อัตราแลกเปลี่ยน guanine Rac Tiam (ผ่านเปิดใช้งานภายในของ phosphoinositide 3-kinase (PI3K), และ Vav2 Tiam และ Rac ที่สามารถเป็นภาษาท้องถิ่นที่ junctions ยังผ่านขั้วพาร์ซับซ้อน (ไม่แสดงในภาพ) [17] ครอ inhibitors ได้แก่ CCM2 (เชื่อมโยงผ่าน CCM1 และβ-catenin และควบคุมลงครอกิจกรรมผ่านกลไกยังกำหนดไม่ดี) และ p190RhoGAP (เชื่อมโยงผ่าน p120) Rap1 สามารถถ่ายทอดสัญญาณจากค่าย ผ่านของ GEF, Epac [8] ดังนั้น เฉพาะคลัสเตอร์ของ VE cadherin เป็นข้อบังคับของสมาคมβ catenin และ p120 กับ VE cadherin แล้วการชุมนุมของหน่วยระดับโมเลกุลที่ควบคุมการ polymerization แอกตินและการหดตัวที่ junctions เครื่องมือ pharmacological การ modulate ที่ซับซ้อนอาจจะเป็นเกี่ยวข้องรักษาA crucial molecule in the organization of actin at the adherens junctions is α-catenin. The molecular features of the relationship between α-catenin and actin have been profoundly revised in recent years (reviewed in [6]). Instead of a 'simple' bridge between junctional cadherin and the actin microfilament cytoskeleton, α-catenin is now considered to act as a regulator of actin polymerization. For allosteric reasons α-catenin cannot bind at the same time to β-catenin and actin filaments. Dimeric α-catenin binds with high affinity to actin filaments, and inhibiting Arp2/3 activity suppresses actin branching. In addition, dimeric α-catenin promotes the formation of linear actin cables by activating formin (Figure 2; [6] and references therein).If α-catenin is not the tether between VE-cadherin and actin, which junctional components might be? This is not known at present. Afadin, a cytoplasmic molecule localized at adherens junctions bound to the nectin adhesive receptors, can anchor actin to the plasma membrane and could contribute to the stabilization of the peripheral actin rim [5,6]. Which other junctional components might tether actin filaments to adherens junctions remains to be determined.In addition, β-catenin has an important role in regulating the behavior of actin. Small GTPases of the Rho family that have crucial effects on the control of actin polymerization [4] and on the contractility of actomyosin are recruited and regulated at adherens junctions through β-catenin (Figure 2; see [7] for a comprehensive review of the roles of these GTPases in epithelial cells).Remodeling or de novo polymerization of actin filaments can be controlled by the GTPases Rac and Rho, while Rho also affects the contractility of actomyosin, the complex of actin and myosin that makes up the contractile stress fibers. Rac signaling at adherens junctions is likely to be downstream of the small GTPase Rap1 [8], which in endothelial cells can be localized at adherens junctions in a complex with VE-cadherin through CCM1 and β-catenin [9]. In addition, Rap1 can be activated at junctions by PDZ-GEF, recruited locally by the protein MAGI, which is linked to VE-cadherin through β-catenin [10]. Rap1 can also convey signals from cAMP, through its guanine nucleotide exchange factor (GEF) Epac, to stabilize the barrier properties of the endothe
การแปล กรุณารอสักครู่..
Endothelial adherens junctions and the actin cytoskeleton: an 'infinity net'?
Abstract
A recent paper in BMC Biology reports that actin stress fibers in adjacent cultured endothelial cells are linked through adherens junctions. This organization might provide a super-cellular network that could enable coordinated signaling and structural responses in endothelia.
See research article http://www.biomedcentral.com/1741-7007/8/11 webcite
Minireview
The title of this minireview is inspired by the work of the Japanese artist Yayoi Kusama, who paints wonderful networks as one of her favorite subjects. As an artist, she can evoke images and concepts that are sometimes beyond her own knowledge: in this case her idea of a continuous network well suits a model of intercellular cytoskeletal linking suggested by a recent paper published in BMC Biology by Millan et al. [1]. Working with cultured human umbilical cord vein endothelial cells they find that actin-based stress fibers in adjacent endothelial cells in confluent culture can become linked through adherens junctions. This organization could, in theory, enable a communication network extending throughout the endothelium, as well as maintaining structural coherence and increasing resistance to stress. This capacity could be crucial to the function and adaptability of the endothelium, which is continuously exposed to changes in blood flow, whether in normal physiologic situations, or during inflammation or angiogenesis.
This is a novel extension of a concept first used for epithelial sheets [2] to endothelial monolayers.
The adherens junction
The intercellular junctions between endothelial cells maintain endothelial integrity, controlling the movement of solutes between bloodstream and tissues, and the flow of white blood cells between blood and tissues, especially at sites of infection and inflammation. Adherens junctions both mediate adhesion between cells and support the local concentration of scaffolding and signaling molecules. This enables molecular interactions that otherwise would not take place and the segregation of signaling molecules for specific regulation (for a general description of the organization of cell-cell contacts in endothelial cells see [3]). Adherens junctions are based on the transmembrane adhesive receptor that belongs to the cadherin family and a notable and specific feature of the endothelial junctions is the presence of the tissue-specific vascular endothelial (VE)-cadherin. VE-cadherin is constitutively linked through its cytoplasmic tail directly to β- or γ-catenin (plakoglobin) or the catenin p120, and indirectly to α-catenin via β- or γ-catenin.
From studies in epithelial and endothelial cells, the conventional view of adherens junctions is that they link through the catenin complex to cortical actin filaments that lie parallel to the cell surface. In their confluent endothelial cell cultures, however, Millan et al. [1] found an additional type of adherens junction organization. They found that staining for junctional components such as VE-cadherin revealed lines of staining running in from the cell surface rather than lying parallel to the cell surface as in conventional adherens junction complexes. The authors call these novel junctions 'discontinuous adherens junctions' to distinguish them from those more familiar from epithelial cells. Further staining for VE-cadherin and actin revealed that actin stress fibers running perpendicular to the cell surface were associated with these discontinuous adherens junctions (Figure 1).
Figure 1. Structural and functional actin filament organization at cell-cell junctions in endothelial cells. In quiescent cells, junctional actin filaments can be oriented either parallel (left-hand image) or perpendicular (center image) to the cell surface. A question mark indicates that it is not known whether these two types of arrangement can interchange, or whether the perpendicular arrangement must arise de novo. Actomyosin stress fibers are anchored to the membrane through adherens junctions[1]. VE-cadherin is required, but the stress fibers are not directly linked to the cadherin-catenin complex. They are possibly tethered to adherens junctions by afadin or other, still unidentified molecules (see Figure 2, and text for details). Subdomains with perpendicular actin fibers, called 'discontinuous adherens junctions' in [1], are dynamic, and undergo constant reorganization. In these areas, actin fibers of adjoining cells are connected through adherens junctions into a supercellular network [1]. In quiescent endothelial cells, actin stress fibers are polymerized through the action of Rac and Rho, Rho signaling through the actin nucleator Dia (diaphanous-related formin) [7]. Various stimuli activate the endothelium and induce actomyosin contraction at the dynamic domains (right-hand image), with Rho signaling through the protein kinase ROCK [7], and resulting in the opening of intercellular gaps, making the endothelium permeable to fluid and molecules, and facilitating the transmigration of leukocytes. In activated conditions, adherens junctions are also functionally and structurally modified (indicated by the change of the junctional symbol to blue). The molecular details of such alterations are still incompletely understood. The association of actin with adherens junctions is also likely to be modified. It remains to be defined at which molecules/structures (indicated by question marks) anchor the actin fibers at the ends that are not interacting with the adherens junction. This anchoring is critical to allow productive contraction.
Local regulation of actin by adherens junctions in endothelial cells
At early phases of junction formation, actin filaments organize perpendicularly to the membrane through the local accumulation of actin-nucleating complexes [4]. Further stages of junction maturation are accompanied by the development of actin fibers parallel to the membrane to form a peripheral actin rim ([5] and references therein). It is not clear at present whether the perpendicular actin fibers described by Millan et al. [1] are residual early fibers or derive by de novo organization. Actin reorganization at cell-cell junctions proceeds through the action of several regulators that concentrate locally (Figure 2).
Figure 2. Schematic representation of some signaling networks that control the formation of actin stress fibers at adherens junctions in endothelial cells. VE-cadherin can directly or indirectly recruit regulators of actin polymerization, among which is the small GTPase Rac as well as regulators of Rac and Rho. Regulators include Rac activators, such as the small GPTPase Rap1 (linked through CCM1 and β-catenin) and its guanine-exchange factor, PDZ-GEF (linked through MAGI and β-catenin), the Rac guanine-exchange factor Tiam (through the local activation of phosphoinositide 3-kinase (PI3K), and Vav2. Tiam and Rac can be localized at junctions also through the Par polarity complex (not shown in the figure) [17]. Rho inhibitors include CCM2 (linked through CCM1 and β-catenin and down-regulating Rho activity through a still poorly defined mechanism) and p190RhoGAP (linked through p120). Rap1 can convey signals from cAMP, through its GEF, Epac [8]. Therefore, local clustering of VE-cadherin as well as regulation of the association of β-catenin and p120 to VE-cadherin appears crucial to the assembly of a molecular unit controlling actin polymerization and contraction at junctions. Pharmacological tools to modulate this complex might be of therapeutic relevance.
A crucial molecule in the organization of actin at the adherens junctions is α-catenin. The molecular features of the relationship between α-catenin and actin have been profoundly revised in recent years (reviewed in [6]). Instead of a 'simple' bridge between junctional cadherin and the actin microfilament cytoskeleton, α-catenin is now considered to act as a regulator of actin polymerization. For allosteric reasons α-catenin cannot bind at the same time to β-catenin and actin filaments. Dimeric α-catenin binds with high affinity to actin filaments, and inhibiting Arp2/3 activity suppresses actin branching. In addition, dimeric α-catenin promotes the formation of linear actin cables by activating formin (Figure 2; [6] and references therein).
If α-catenin is not the tether between VE-cadherin and actin, which junctional components might be? This is not known at present. Afadin, a cytoplasmic molecule localized at adherens junctions bound to the nectin adhesive receptors, can anchor actin to the plasma membrane and could contribute to the stabilization of the peripheral actin rim [5,6]. Which other junctional components might tether actin filaments to adherens junctions remains to be determined.
In addition, β-catenin has an important role in regulating the behavior of actin. Small GTPases of the Rho family that have crucial effects on the control of actin polymerization [4] and on the contractility of actomyosin are recruited and regulated at adherens junctions through β-catenin (Figure 2; see [7] for a comprehensive review of the roles of these GTPases in epithelial cells).
Remodeling or de novo polymerization of actin filaments can be controlled by the GTPases Rac and Rho, while Rho also affects the contractility of actomyosin, the complex of actin and myosin that makes up the contractile stress fibers. Rac signaling at adherens junctions is likely to be downstream of the small GTPase Rap1 [8], which in endothelial cells can be localized at adherens junctions in a complex with VE-cadherin through CCM1 and β-catenin [9]. In addition, Rap1 can be activated at junctions by PDZ-GEF, recruited locally by the protein MAGI, which is linked to VE-cadherin through β-catenin [10]. Rap1 can also convey signals from cAMP, through its guanine nucleotide exchange factor (GEF) Epac, to stabilize the barrier properties of the endothe
Abstract
A recent paper in BMC Biology reports that actin stress fibers in adjacent cultured endothelial cells are linked through adherens junctions. This organization might provide a super-cellular network that could enable coordinated signaling and structural responses in endothelia.
See research article http://www.biomedcentral.com/1741-7007/8/11 webcite
Minireview
The title of this minireview is inspired by the work of the Japanese artist Yayoi Kusama, who paints wonderful networks as one of her favorite subjects. As an artist, she can evoke images and concepts that are sometimes beyond her own knowledge: in this case her idea of a continuous network well suits a model of intercellular cytoskeletal linking suggested by a recent paper published in BMC Biology by Millan et al. [1]. Working with cultured human umbilical cord vein endothelial cells they find that actin-based stress fibers in adjacent endothelial cells in confluent culture can become linked through adherens junctions. This organization could, in theory, enable a communication network extending throughout the endothelium, as well as maintaining structural coherence and increasing resistance to stress. This capacity could be crucial to the function and adaptability of the endothelium, which is continuously exposed to changes in blood flow, whether in normal physiologic situations, or during inflammation or angiogenesis.
This is a novel extension of a concept first used for epithelial sheets [2] to endothelial monolayers.
The adherens junction
The intercellular junctions between endothelial cells maintain endothelial integrity, controlling the movement of solutes between bloodstream and tissues, and the flow of white blood cells between blood and tissues, especially at sites of infection and inflammation. Adherens junctions both mediate adhesion between cells and support the local concentration of scaffolding and signaling molecules. This enables molecular interactions that otherwise would not take place and the segregation of signaling molecules for specific regulation (for a general description of the organization of cell-cell contacts in endothelial cells see [3]). Adherens junctions are based on the transmembrane adhesive receptor that belongs to the cadherin family and a notable and specific feature of the endothelial junctions is the presence of the tissue-specific vascular endothelial (VE)-cadherin. VE-cadherin is constitutively linked through its cytoplasmic tail directly to β- or γ-catenin (plakoglobin) or the catenin p120, and indirectly to α-catenin via β- or γ-catenin.
From studies in epithelial and endothelial cells, the conventional view of adherens junctions is that they link through the catenin complex to cortical actin filaments that lie parallel to the cell surface. In their confluent endothelial cell cultures, however, Millan et al. [1] found an additional type of adherens junction organization. They found that staining for junctional components such as VE-cadherin revealed lines of staining running in from the cell surface rather than lying parallel to the cell surface as in conventional adherens junction complexes. The authors call these novel junctions 'discontinuous adherens junctions' to distinguish them from those more familiar from epithelial cells. Further staining for VE-cadherin and actin revealed that actin stress fibers running perpendicular to the cell surface were associated with these discontinuous adherens junctions (Figure 1).
Figure 1. Structural and functional actin filament organization at cell-cell junctions in endothelial cells. In quiescent cells, junctional actin filaments can be oriented either parallel (left-hand image) or perpendicular (center image) to the cell surface. A question mark indicates that it is not known whether these two types of arrangement can interchange, or whether the perpendicular arrangement must arise de novo. Actomyosin stress fibers are anchored to the membrane through adherens junctions[1]. VE-cadherin is required, but the stress fibers are not directly linked to the cadherin-catenin complex. They are possibly tethered to adherens junctions by afadin or other, still unidentified molecules (see Figure 2, and text for details). Subdomains with perpendicular actin fibers, called 'discontinuous adherens junctions' in [1], are dynamic, and undergo constant reorganization. In these areas, actin fibers of adjoining cells are connected through adherens junctions into a supercellular network [1]. In quiescent endothelial cells, actin stress fibers are polymerized through the action of Rac and Rho, Rho signaling through the actin nucleator Dia (diaphanous-related formin) [7]. Various stimuli activate the endothelium and induce actomyosin contraction at the dynamic domains (right-hand image), with Rho signaling through the protein kinase ROCK [7], and resulting in the opening of intercellular gaps, making the endothelium permeable to fluid and molecules, and facilitating the transmigration of leukocytes. In activated conditions, adherens junctions are also functionally and structurally modified (indicated by the change of the junctional symbol to blue). The molecular details of such alterations are still incompletely understood. The association of actin with adherens junctions is also likely to be modified. It remains to be defined at which molecules/structures (indicated by question marks) anchor the actin fibers at the ends that are not interacting with the adherens junction. This anchoring is critical to allow productive contraction.
Local regulation of actin by adherens junctions in endothelial cells
At early phases of junction formation, actin filaments organize perpendicularly to the membrane through the local accumulation of actin-nucleating complexes [4]. Further stages of junction maturation are accompanied by the development of actin fibers parallel to the membrane to form a peripheral actin rim ([5] and references therein). It is not clear at present whether the perpendicular actin fibers described by Millan et al. [1] are residual early fibers or derive by de novo organization. Actin reorganization at cell-cell junctions proceeds through the action of several regulators that concentrate locally (Figure 2).
Figure 2. Schematic representation of some signaling networks that control the formation of actin stress fibers at adherens junctions in endothelial cells. VE-cadherin can directly or indirectly recruit regulators of actin polymerization, among which is the small GTPase Rac as well as regulators of Rac and Rho. Regulators include Rac activators, such as the small GPTPase Rap1 (linked through CCM1 and β-catenin) and its guanine-exchange factor, PDZ-GEF (linked through MAGI and β-catenin), the Rac guanine-exchange factor Tiam (through the local activation of phosphoinositide 3-kinase (PI3K), and Vav2. Tiam and Rac can be localized at junctions also through the Par polarity complex (not shown in the figure) [17]. Rho inhibitors include CCM2 (linked through CCM1 and β-catenin and down-regulating Rho activity through a still poorly defined mechanism) and p190RhoGAP (linked through p120). Rap1 can convey signals from cAMP, through its GEF, Epac [8]. Therefore, local clustering of VE-cadherin as well as regulation of the association of β-catenin and p120 to VE-cadherin appears crucial to the assembly of a molecular unit controlling actin polymerization and contraction at junctions. Pharmacological tools to modulate this complex might be of therapeutic relevance.
A crucial molecule in the organization of actin at the adherens junctions is α-catenin. The molecular features of the relationship between α-catenin and actin have been profoundly revised in recent years (reviewed in [6]). Instead of a 'simple' bridge between junctional cadherin and the actin microfilament cytoskeleton, α-catenin is now considered to act as a regulator of actin polymerization. For allosteric reasons α-catenin cannot bind at the same time to β-catenin and actin filaments. Dimeric α-catenin binds with high affinity to actin filaments, and inhibiting Arp2/3 activity suppresses actin branching. In addition, dimeric α-catenin promotes the formation of linear actin cables by activating formin (Figure 2; [6] and references therein).
If α-catenin is not the tether between VE-cadherin and actin, which junctional components might be? This is not known at present. Afadin, a cytoplasmic molecule localized at adherens junctions bound to the nectin adhesive receptors, can anchor actin to the plasma membrane and could contribute to the stabilization of the peripheral actin rim [5,6]. Which other junctional components might tether actin filaments to adherens junctions remains to be determined.
In addition, β-catenin has an important role in regulating the behavior of actin. Small GTPases of the Rho family that have crucial effects on the control of actin polymerization [4] and on the contractility of actomyosin are recruited and regulated at adherens junctions through β-catenin (Figure 2; see [7] for a comprehensive review of the roles of these GTPases in epithelial cells).
Remodeling or de novo polymerization of actin filaments can be controlled by the GTPases Rac and Rho, while Rho also affects the contractility of actomyosin, the complex of actin and myosin that makes up the contractile stress fibers. Rac signaling at adherens junctions is likely to be downstream of the small GTPase Rap1 [8], which in endothelial cells can be localized at adherens junctions in a complex with VE-cadherin through CCM1 and β-catenin [9]. In addition, Rap1 can be activated at junctions by PDZ-GEF, recruited locally by the protein MAGI, which is linked to VE-cadherin through β-catenin [10]. Rap1 can also convey signals from cAMP, through its guanine nucleotide exchange factor (GEF) Epac, to stabilize the barrier properties of the endothe
การแปล กรุณารอสักครู่..
ทางแยก adherens บุและ actin ขาดตอน : ' อินฟินิตี้สุทธิ "
เป็นนามธรรมกระดาษล่าสุดใน BMC ชีววิทยารายงานว่าเส้นใย actin ความเครียดในเซลล์เพาะเลี้ยงเยื่อข้างเคียงมีการเชื่อมโยงผ่าน adherens ทางแยก องค์กรนี้จะให้ Super เครือข่ายมือถือที่สามารถช่วยประสานงานการส่งสัญญาณและการตอบสนองโครงสร้างบทความวิจัย endothelia .
ดู http : / / www .biomedcentral.com/1741-7007/8/11 minireview webcite
ชื่อ minireview นี้เป็นแรงบันดาลใจจากผลงานของศิลปินญี่ปุ่น ยาโยอิ คุซาม่าที่สีเครือข่ายที่ยอดเยี่ยมเป็นหนึ่งในวิชาที่เธอชื่นชอบ เป็นศิลปิน เธอสามารถทำให้ภาพและแนวคิดที่บางครั้งอยู่นอกเหนือความรู้ของเธอเองในกรณีนี้แนวคิดของเครือข่ายอย่างต่อเนื่องได้ดีเหมาะกับรูปแบบของการเชื่อมโยงซึ่งอยู่ระหว่างเซลล์ไซโตร กเลตัลแนะนำโดยล่าสุดกระดาษที่ตีพิมพ์ใน BMC ชีววิทยาโดย Millan et al . [ 1 ] การทำงานกับหลอดเลือดดำสายสะดือสายสะดือมนุษย์ endothelial เซลล์เพาะเลี้ยงพบว่าเส้นใย actin ความเครียด ในเซลล์เยื่อบุหลอดเลือดที่อยู่ติดกันในวัฒนธรรมกระจู๋กระจี๋สามารถกลายเป็นที่เชื่อมโยงผ่าน adherens ทางแยกองค์กรนี้ได้ ในทางทฤษฎี ช่วยให้หลอดเลือดขยายทั่วทั้งเครือข่ายการสื่อสาร ตลอดจนการรักษาโครงสร้างและเพิ่มการต้านทานความเครียด ความสามารถนี้อาจจะสำคัญในการทำงานและการปรับตัวของหลอดเลือดซึ่งเป็นอย่างต่อเนื่องได้รับการเปลี่ยนแปลงในการไหลของเลือด ไม่ว่าในสถานการณ์ปกติปกติหรือระหว่างการอักเสบหรือเจเนซิส
นี้เป็นส่วนขยายใหม่ของแนวคิดแรกที่ใช้สำหรับแผ่นบุ [ 2 ] เพื่อบุ monolayers .
adherens ชุมทางเชื่อมระหว่างเยื่อบุเซลล์ intercellular รักษาความสมบูรณ์ของการควบคุมการเคลื่อนไหวของสารระหว่างเลือดและเนื้อเยื่อ และการไหลของเลือดและเซลล์เลือดขาวระหว่างเนื้อเยื่อ ,โดยเฉพาะในเว็บไซต์ของการติดเชื้อและการอักเสบ adherens เชื่อมยึดระหว่างเซลล์ทั้งสองไกล่เกลี่ยและสนับสนุนท้องถิ่นของนั่งร้านและความเข้มข้นของสัญญาณโมเลกุลนี้จะช่วยให้การปฏิสัมพันธ์โมเลกุลที่เป็นอย่างอื่นจะไม่เกิดขึ้น และการส่งสัญญาณโมเลกุลสำหรับกฎระเบียบที่เฉพาะเจาะจง ( สำหรับรายละเอียดทั่วไปขององค์กรของผู้ติดต่อในเยื่อบุเซลล์ astrocytoma พบ [ 3 ] )
เป็นนามธรรมกระดาษล่าสุดใน BMC ชีววิทยารายงานว่าเส้นใย actin ความเครียดในเซลล์เพาะเลี้ยงเยื่อข้างเคียงมีการเชื่อมโยงผ่าน adherens ทางแยก องค์กรนี้จะให้ Super เครือข่ายมือถือที่สามารถช่วยประสานงานการส่งสัญญาณและการตอบสนองโครงสร้างบทความวิจัย endothelia .
ดู http : / / www .biomedcentral.com/1741-7007/8/11 minireview webcite
ชื่อ minireview นี้เป็นแรงบันดาลใจจากผลงานของศิลปินญี่ปุ่น ยาโยอิ คุซาม่าที่สีเครือข่ายที่ยอดเยี่ยมเป็นหนึ่งในวิชาที่เธอชื่นชอบ เป็นศิลปิน เธอสามารถทำให้ภาพและแนวคิดที่บางครั้งอยู่นอกเหนือความรู้ของเธอเองในกรณีนี้แนวคิดของเครือข่ายอย่างต่อเนื่องได้ดีเหมาะกับรูปแบบของการเชื่อมโยงซึ่งอยู่ระหว่างเซลล์ไซโตร กเลตัลแนะนำโดยล่าสุดกระดาษที่ตีพิมพ์ใน BMC ชีววิทยาโดย Millan et al . [ 1 ] การทำงานกับหลอดเลือดดำสายสะดือสายสะดือมนุษย์ endothelial เซลล์เพาะเลี้ยงพบว่าเส้นใย actin ความเครียด ในเซลล์เยื่อบุหลอดเลือดที่อยู่ติดกันในวัฒนธรรมกระจู๋กระจี๋สามารถกลายเป็นที่เชื่อมโยงผ่าน adherens ทางแยกองค์กรนี้ได้ ในทางทฤษฎี ช่วยให้หลอดเลือดขยายทั่วทั้งเครือข่ายการสื่อสาร ตลอดจนการรักษาโครงสร้างและเพิ่มการต้านทานความเครียด ความสามารถนี้อาจจะสำคัญในการทำงานและการปรับตัวของหลอดเลือดซึ่งเป็นอย่างต่อเนื่องได้รับการเปลี่ยนแปลงในการไหลของเลือด ไม่ว่าในสถานการณ์ปกติปกติหรือระหว่างการอักเสบหรือเจเนซิส
นี้เป็นส่วนขยายใหม่ของแนวคิดแรกที่ใช้สำหรับแผ่นบุ [ 2 ] เพื่อบุ monolayers .
adherens ชุมทางเชื่อมระหว่างเยื่อบุเซลล์ intercellular รักษาความสมบูรณ์ของการควบคุมการเคลื่อนไหวของสารระหว่างเลือดและเนื้อเยื่อ และการไหลของเลือดและเซลล์เลือดขาวระหว่างเนื้อเยื่อ ,โดยเฉพาะในเว็บไซต์ของการติดเชื้อและการอักเสบ adherens เชื่อมยึดระหว่างเซลล์ทั้งสองไกล่เกลี่ยและสนับสนุนท้องถิ่นของนั่งร้านและความเข้มข้นของสัญญาณโมเลกุลนี้จะช่วยให้การปฏิสัมพันธ์โมเลกุลที่เป็นอย่างอื่นจะไม่เกิดขึ้น และการส่งสัญญาณโมเลกุลสำหรับกฎระเบียบที่เฉพาะเจาะจง ( สำหรับรายละเอียดทั่วไปขององค์กรของผู้ติดต่อในเยื่อบุเซลล์ astrocytoma พบ [ 3 ] )
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