DYSTROPHINS IN VERTEBRATES AND INVERTEBRATES

Members of the dystrophin family of proteins perform a critical but in completely characterized role in the maintenance of membrane-associate d complexes at points of intercellular contact in many vertebrate cell types. They interact with, amongst others, the transmembrane laminin receptor dystroglycan, cytoskeletal actin and, indirectly, the intrace llular membrane-associated signalling enzyme neuronal nitric oxide syn thase (nNOS). Here we describe sequences of a range of dystrophin-rela ted proteins from vertebrate and invertebrate animals (including the i mportant model organism Drosophila melanogaster) and infer an evolutio nary history of this family and its relationship to the distantly rela ted dystrobrevins. It appears that most metazoa possess sequences enco ding a single highly conserved dystrophin-like protein in addition to a presumed distinct dystrobrevin, derived from an early duplication of an ancestral gene. In the vertebrates (but not the protochordate Amph ioxus), the single invertebrate dystrophin-like gene has undergone ser ial duplication to generate at least three distinct genes encoding pro teins which have adopted specialized roles. It is hoped that this broa dening of the biology of the dystrophins will afford further opportuni ties for the advancement of our understanding of the fundamental defec t underlying the variety of human genetic disorders which result from aberrant or absent dystrophin-associated complexes.