Identification and purification of an agrin receptor from Torpedo postsynaptic membranes: a heteromeric complex related to the dystroglycans.
The selective concentration of neurotransmitter receptors at the postsynaptic membrane is an essential aspect of synaptic differentiation and function. Agrin is an extracellular matrix protein that is likely to direct the accumulation of acetylcholine receptors and several other postsynaptic elements at developing and regenerating neuromuscular junctions. How agrin interacts with the membrane to bring about these changes is unknown. We now report the identification and purification of a protein complex from Torpedo electric organ postsynaptic membranes that is likely to serve as an agrin receptor. The native receptor is a heteromeric complex of two membrane glycoproteins of 190 kDa and 50 kDa. The 190 kDa subunit is sufficient to bind ligand. Peptide sequence analysis revealed that the 190 kDa and 50 kDa subunits are related to the dystrophin-associated glycoproteins alpha- and beta-dystroglycan, respectively. No other candidate agrin receptors were detected. The identification of the agrin receptor opens new avenues toward a mechanistic understanding of synapse differentiation.
Bowe
M A
MA
Neurobiology Group, Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts 01545.
Deyst
K A
KA
Leszyk
J D
JD
Fallon
J R
JR
D018171:Agrin / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D002462:Cell Membrane / Q000378:metabolism; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D003598:Cytoskeletal Proteins / Q000737:chemistry*; D049030:Dystroglycans; D016189:Dystrophin / Q000737:chemistry; D004557:Electric Organ / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015151:Immunoblotting; D008562:Membrane Glycoproteins / Q000737:chemistry*; D051379:Mice / Q000276:immunology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D010449:Peptide Mapping; D017978:Receptors, Growth Factor / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013569:Synapses; D014101:Torpedo
D018171:Agrin; D000911:Antibodies, Monoclonal; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D017978:Receptors, Growth Factor; C080030:agrin receptor; D049030:Dystroglycans