Spectrin: a structural mediator between diverse plasma membrane proteins and the cytoplasm

The spectrin skeleton of non-erythroid cells is likely to interact with a variety of integral membrane proteins and participate both in stable linkages as well as dynamic structures capable of rapid disassembly and assembly. The basis for diversity of roles for spectrin includes multiple, functionally distinct isoforms of spectrin, ankyrin and other associated proteins, regulation of protein interactions through phosphorylation and calcium/calmodulin, as well as differential expression of accessory proteins that determine the organization and localization of spectrin in cells. Spectrin is highly conserved from Drosophila to man and is likely to be involved in fundamental aspects of membrane structure requiring long range order and organization. Spectrin is a candidate to interact with many integral membrane proteins in roles basic to metazoan cells which must associate into tissues. Organization of cells into tissues requires loss of cell motility, formation of specialized membrane domains and assembly of cell junctions, which are all activities potentially involving spectrin. Future challenges lie in devising direct experiments to evaluate the functions of spectrin in cells and tissues.