Electric tissue syntrophin, originally described as an M(r) 58,000 postsynaptic protein having homologs in mammalian muscle, was previously shown to associate with dystrophin in Triton extracts of Torpedo postsynaptic membranes. It also associates with the Torpedo M(r) 87,000 postsynaptic protein (87K), the core of which is a superdomain homologous to the cysteine-rich (CR) and COOH-terminal (CT) domains of human dystrophin. Using immunoaffinity purifications from various rat tissues and immunoblotting, we find that syntrophin associates with dystrophin, utrophin (the chromosome 6-encoded dystrophin homolog formerly known as dystrophin-related protein), multiple proteins which are cross-reactive with 87K, and two subfamilies of 71K-like proteins (CRCT-containing proteins encoded by the dystrophin gene under the control of an alternative promoter in intron 62). One 71K subfamily retains the dystrophin COOH-terminal sequence; the other has an alternative COOH-terminal sequence caused by deletion of the penultimate exon by alternative splicing. The relative masses of the members of the subfamilies suggest they arise by alternative splicing at other previously described sites within CT. These results establish that syntrophin is a general ligand for the CRCT domain in mammalian dystrophin and its homologs. They also reveal a greater diversity in 71K proteins than has previously been apparent
