Regulation of acetylcholine receptor clustering by the tumor suppressor APC.
At the developing neuromuscular junction, motor neuron-derived agrin triggers the differentiation of postsynaptic membrane into a highly specialized structure, where the nicotinic acetylcholine receptors (AChRs) are aggregated into high-density clusters. Agrin acts by activating the muscle-specific kinase MuSK and inducing coaggregation of the 43-kDa protein rapsyn with AChRs on muscle cell membrane. The signaling mechanism downstream of MuSK is poorly defined. We report here that the mouse tumor suppressor protein adenomatous polyposis coli (APC) has a role in AChR clustering and that the Wnt/beta-catenin pathway may crosstalk with agrin signaling cascade during synapse formation.
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D018171:Agrin / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology / Q000294:innervation* / Q000378:metabolism; D009469:Neuromuscular Junction / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011940:Receptor Aggregation / Q000187:drug effects / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; D018171:Agrin; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C475048:MuSK protein, rat; D020794:Receptor Protein-Tyrosine Kinases