Cells of multicellular organisms have evolved highly organized plasma membranes with the capacity to participate in diverse functions, such as formation of cell-cell junctions, localized flux of ions, and polarized secretion of intracellular vesicles. Functions of the plasma membrane requiring mechanical stability and long-range order cannot be explained by a simple model of integral membrane proteins embedded in a fluid phospholipid bilayer. A general conclusion from the last two decades of membrane research is that many integral membrane proteins are directly linked to proteins on the cytoplasmic surface of the plasma membrane and that membrane-cytoskeletal linkages are responsible for much of the organization of the plasma membrane. Plasma membranes may contain a common structural system capable of association with diverse membrane proteins. In support of a generalized membrane structure are the findings that many different membrane proteins exhibit restricted translational mobility (78, 199,353) and relocate to the same areas of plasma membranes (55).

A system of membrane-associated structural proteins, referred to as the spectrin-based membrane skeleton, is a candidate for a role as a ubiquitous membrane structure capable of interacting with a variety of integral membrane proteins. The spectrin-based membrane skeleton was first characterized in human erythrocytes where it associates through defined protein interactions with integral membrane proteins and forms a meshwork on the cytoplasmic surface of the plasma membrane. Spectrin, an extended rod-shaped protein, is the principal protein of the membrane skeleton and is assembled into a two-dimensional network with the assistance of actin and other accessory proteins. The principal function of the spectrin skeleton in erythrocytes is to provide structural support for the lipid bilayer, and this structure is essential for prolonged survival of erythrocytes in the high-shear environment of the vascular sys-