Figure 9.2. The secretory pathway Pancreatic acinar cells, which secrete most of their newly synthesized proteins into the digestive tract, were labeled with radioactive amino acids to study the intracellular pathway taken by secreted proteins. After a short incubation with radioactive amino acids (3-minute label), autoradiography revealed that newly synthesized proteins were localized to the rough ER. Following further incubation with nonradioactive amino acids (a chase), proteins were found to move from the ER to the Golgi apparatus and then, within secretory vesicles, to the plasma membrane and cell exterior.
These investigators studied the fate of newly synthesized proteins in specialized cells of the pancreas (pancreatic acinar cells) that secrete digestive enzymes into the small intestine. Because most proteins synthesized by these cells are secreted, Palade and coworkers were able to study the pathway taken by secreted proteins simply by labeling newly synthesized proteins with radioactive amino acids. The location of the radiolabeled proteins within the cell was then determined by autoradiography, revealing the cellular sites involved in the events leading to protein secretion. After a brief exposure of pancreatic acinar cells to radioactive amino acids, newly synthesized proteins were detected in the rough ER, which was therefore identified as the site of synthesis of proteins destined for secretion. If the cells were then incubated for a short time in media containing nonradioactive amino acids (a process known as a chase), the radiolabeled proteins were detected in the Golgi apparatus. Following longer chase periods, the radiolabeled proteins traveled from the Golgi apparatus to the cell surface in secretory vesicles, which then fused with the plasma membrane to release their contents outside of the cell.
These experiments defined a pathway taken by secreted proteins, the secretory pathway: rough ER Golgi secretory vesicles cell exterior. Further studies extended these results and demonstrated that this pathway is not restricted to proteins destined for secretion from the cell. Plasma membrane and lysosomal proteins also travel from the rough ER to the Golgi and then to their final destinations. Still other proteins travel through the initial steps of the secretory pathway but are then retained and function within either the ER or the Golgi apparatus.