Evolution of the spectrin-based membrane skeleton

Abstract

A group of four proteins - spectrin, ankyrin, 4.1 and adducin - evolved with the metazoa. These membrane-cytoskeletal proteins cross-link actin on the cytoplasmic face of plasma membranes and link a variety of transmembrane proteins to the cytoskeleton. In this paper, the evolution of these proteins is analysed. Genomics indicate that spectrin was the first to appear, since the genome of the choanoflagellate Monosiga brevicolis contains genes for alpha, beta and betaH spectrin. This organism represents a lineage of free-living and colonial protists from which the metazoa are considered to have diverged. This indicates that spectrin emerged in evolution before the animals. Simple animals such as the placozoan Trichoplax adherens also contain recognizable precursors of 4.1, ankyrin and adducin, but these could probably not bind spectrin. Ankyrin and adducin seem to have acquired spectrin-binding activity with the appearance of tissues since they appear to have largely the same domain structure in all eumetazoa. 4.1 was adapted more recently, with the emergence of the vertebrates, to bind spectrin and promote its interaction with actin. A simple hypothesis is that spectrin was prerequisite (but not sufficient) for animal life; that spectrin interaction with ankyrin and adducin was required for evolution of major tissues; and that 4.1 acquired a spectrin-actin binding activity as animal size increased with the appearance of vertebrates. The spectrin/ankyrin/adducin/4.1 complex represents a remarkable system that underpins animal life; it has been adapted to many different functions at different times during animal evolution.