title: AChR phosphorylation and aggregation induced by an agrin fragment that lacks the binding domain for alpha-dystroglycan.
abstract: Agrin induces both phosphorylation and aggregation of nicotinic acetylcholine receptors (AChRs) when added to myotubes in culture, apparently by binding to a specific receptor on the myotube surface. One such agrin receptor is alpha-dystroglycan, although binding to alpha-dystroglycan appears not to mediate AChR aggregation. To determine whether agrin-induced AChR phosphorylation is mediated by alpha-dystroglycan or by a different agrin receptor, fragments of recombinant agrin that differ in affinity for alpha-dystroglycan were examined for their ability to induce AChR phosphorylation and aggregation in mouse C2 myotubes. The carboxy-terminal 95 kDa agrin fragment agrin-c95(A0B0), which binds to alpha-dystroglycan with high affinity, failed to induce AChR phosphorylation and aggregation. In contrast, agrin-c95(A4B8) which binds less strongly to alpha-dystroglycan, induced both phosphorylation and aggregation, as did a small 21 kDa fragment of agrin, agrin-c21(B8), that completely lacks the binding domain for alpha-dystroglycan. We conclude that agrin-induced AChR phosphorylation and aggregation are triggered by an agrin receptor that is distinct from alpha-dystroglycan.
authors.affiliation: Department of Physiology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
authors.forename: T
authors.initials: T
authors.lastname: Meier
authors.forename: M
authors.initials: M
authors.lastname: Gesemann
authors.forename: V
authors.initials: V
authors.lastname: Cavalli
authors.forename: M A
authors.initials: MA
authors.lastname: Ruegg
authors.forename: B G
authors.initials: BG
authors.lastname: Wallace
mesh_terms: D018171:Agrin / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002645:Chickens; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D049030:Dystroglycans; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D011940:Receptor Aggregation; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D018171:Agrin; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011978:Receptors, Nicotinic; D049030:Dystroglycans; D019000:Phosphotyrosine