title: Agrin is a high-affinity binding protein of dystroglycan in non-muscle tissue.
abstract: Agrin is a basement membrane-associated proteoglycan that induces the formation of postsynaptic specializations at the neuromuscular junction. This activity is modulated by alternative splicing and is thought to be mediated by receptors expressed in muscle fibers. An isoform of agrin 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 variety of non-muscle tissues. Here, we analyzed the tissue distribution of agrin and dystroglycan on the protein level and determined their binding affinities. We found that agrin is most abundant in lung, kidney, 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 binding assay, agrin bound to dystroglycan from lung, kidney, and skeletal muscle with a dissociation constant between 1.8 and 2.2 nM, 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 show that the agrin isoform expressed in non-muscle tissue is a high-affinity binding partner of dystroglycan and they suggest that this interaction, like that between laminin and dystroglycan, may be important for the mechanical integrity of the tissue.
authors.affiliation: Department of Pharmacology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Gesemann
authors.forename: A
authors.initials: A
authors.lastname: Brancaccio
authors.forename: B
authors.initials: B
authors.lastname: Schumacher
authors.forename: M A
authors.initials: MA
authors.lastname: Ruegg
mesh_terms: D018171:Agrin / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002645:Chickens; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D049030:Dystroglycans; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D011485:Protein Binding
chemical_list: D018171:Agrin; D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D049030:Dystroglycans