The actin crosslinking proteins exhibit marked diversity in size and shape and crosslink actin filaments in different ways. Amino acid sequence analysis of many of these proteins has provided clues to the origin of their diversity. Spectrin, a-actinin, ABP-120, ABP-280, fimbrin, and dystrophin share a homologous sequence segment that is implicated as the common actin binding domain. The remainder of each protein consists of repetitive and non-repetitive sequence segments that have been shuffled and multiplied in evolution to produce a variety of proteins that are related in function and in composition, but that differ significantly in structure.
introduction
The actin-based cytoskeleton is thought to play an important role in the structure and motility of nonmuscle cells in addition to its well known role in muscle contraction. The precise arrangement of actin filaments (F-actin) in a given cell type is tailored to the functional requirements of that cell. Single filaments of actin can serve as the track for myosin-based motility, but actin is often crosslinked into isotropic gels (e.g. cortical actin) and into bundles (e.g. the cores of microvilli and stercocilia). The state of actin in a given cell or subcellular domain is in large part a function of its associated actin binding proteins. large numbers of which have been found in extracts of muscle and nonmuscle cells. These proteins are often bivalent mol- ecules that can crosslink actin into gcls or lateral bundles of filaments in vztro, much like the gels and bundles that are observed in cells (reviewed in refs 1,2).
Why are there so many different actin crosslinking proteins? Dcspite their similar behavior in v i m , the function of actin crosslinkers in cells is likely to be far more diverse. In addition to their crosslinking roles. many of these proteins are also responsible for the interactions between actin filaments and other cellular structures such as membranes, Z discs, microtubules. and cell junctions. Diversity also provides for differential regulation, so that calcium and protein cofactors such as calmodulin and protein 4.1 affect the actin