A role for dystrophin-associated glycoproteins and utrophin in agrin-induced AChR clustering.
Synapse formation is characterized by the accumulation of molecules at the site of contact between pre- and postsynaptic cells. Agrin, a protein implicated in the regulation of this process, causes the clustering of acetylcholine receptors (AChRs). Here we characterize an agrin-binding site on the surface of muscle cells, show that this site corresponds to alpha-dystroglycan, and present evidence that alpha-dystroglycan is functionally related to agrin activity. Furthermore, we demonstrate that alpha-dystroglycan and adhalin, components of the dystrophin-associated glycoprotein complex, as well as utrophin, colocalize with agrin-induced AChR clusters. Thus, agrin may function by initiating or stabilizing a synapse-specific membrane cytoskeleton that in turn serves as a scaffold upon which synaptic molecules are concentrated.
Campanelli
J T
JT
Howard Hughes Medical Institute, Department of Molecular and Cellular Physiology, Stanford University, California 94305.
Roberds
S L
SL
Campbell
K P
KP
Scheller
R H
RH
D018171:Agrin / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D049030:Dystroglycans; D016189:Dystrophin / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins; D009132:Muscles / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism*; D049031:Sarcoglycans; D012995:Solubility; D013569:Synapses / Q000378:metabolism; D049411:Utrophin
D018171:Agrin; D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011950:Receptors, Cholinergic; D049031:Sarcoglycans; D049411:Utrophin; D049030:Dystroglycans; D006493:Heparin; D002118:Calcium