Many MF-associated proteins [16] have been described in the nervous system (Table 8-3). In general, a good deal is known about their distribution and function in primary cultures of neurons and glia, but less is known about their role in the mature nervous system. Two that have been characterized more extensively are the major nonactin structural elements of the membrane cytoskeleton: spectrin and ankyrin. Spectrin is a flexible, rod-shaped molecule composed of homologous α and β subunits and was originally characterized as a component of the erythrocyte membrane cytoskeleton. Neurons were the first cell type, other than erythrocytes, that were shown to contain spectrins, and the brain form was initially called fodrin. Spectrin heterodimers align end to end to form tetramers, which are cross-linked by short actin MFs. This spectrin—actin meshwork is tightly coupled to the plasma membrane through direct binding to membrane proteins. Some of these interactions occur via the protein ankyrin, which has separate binding sites for specific membrane proteins and β-spectrin (seeFig. 2-5). In neurons, specific isoforms of spectrin and ankyrin are localized to axons, dendrites and paranodal regions. The spectrin and ankyrin isoforms in perikarya and dendrites tend to be highly homologous to the erythrocyte forms and distinct from the spectrin and ankyrin isoforms that occur in axons.