INTRODUCTION

The spectrin-based membrane skeleton (SBMS) is a remarkably diverse and multifunctional molecular scaffold. This structure was first identified as the primary cytoskeletal element in the erythrocyte, where it is responsible for maintaining cell shape and plasma membrane integrity (Mohandas and Evans, 1994; Tse and Lux, 1999). Now recognized as a ubiquitous structure in metazoan cells, the actual and postulated processes in which the SBMS participates additionally include the generation of specialised membrane domains; polarization of specific proteins in cells; protein sorting; vesicle transport; endocytosis; morphogenesis; and even yet to be characterized nuclear function(s) (De Matteis and Morrow, 2000; Bennett and Baines, 2001; Thomas, 2001; Tse et al., 2001).

Spectrin in the erythrocyte is a heterotetrameric protein comprised of two α- and two β-chains. Each chain is a long, rope-like molecule consisting largely of 106 amino acid triple α-helical repeat units (spectrin repeats), but with specialized protein modules within and at either end of this array (itemized in Figure 11.1). Dimerisation of α- and β-spectrins occurs in an antiparallel fashion and dimer pairs interact via the ‘head-to-head’ interaction to generate tetramers. This arrangement leaves an actin-binding domain at either end of the tetramer, and a major activity of spectrin is to cross-link actin into highly branched networks associated with membrane surfaces (Figure 11.2; Bennett and Baines, 2001).