AGRIN IS A HIGH-AFFINITY BINDING-PROTEIN OF DYSTROGLYCAN IN NONMUSCLETISSUE

Agrin is a basement membrane-associated proteoglycan that induces the formation of postsynaptic specializations at the neuromuscular junctio n, This activity is modulated by alternative splicing and is thought t o be mediated by receptors expressed in muscle fibers, An isoform of a grin that does not induce postsynaptic specializations binds with high affinity to dystroglycan, a component of the dystrophin-glycoprotein complex. Transcripts encoding this agrin isoform are expressed in a va riety of non-muscle tissues, Here, we analyzed the tissue distribution of agrin and dystroglycan on the protein level and determined their b inding affinities, We found that agrin is most abundant in lung, kidne y, and brain, Only a little agrin was detected in skeletal muscle, and no agrin was found in liver, Dystroglycan was highly expressed in all tissues examined except in liver, In a solid-phase radioligand bindin g assay, agrin bound to dystroglycan from lung, kidney, and skeletal m uscle with a dissociation constant between 1.8 and 2.2 nar, while the affinity to brain-derived dystroglycan was 4.6 nM. In adult kidney and lung, agrin co-purified and co-immunoprecipitated with dystroglycan, and both molecules were co-localized in embryonic tissue, These data s how that the agrin isoform expressed in non-muscle tissue is a high-af finity binding partner of dystroglycan and they suggest that this inte raction, like that between laminin and dystroglycan, may be important for the mechanical integrity of the tissue.