PMID- 15159418 OWN - NLM STAT- MEDLINE DCOM- 20040909 LR - 20181113 IS - 0021-9525 (Print) IS - 1540-8140 (Electronic) IS - 0021-9525 (Linking) VI - 165 IP - 4 DP - 2004 May 24 TI - MuSK is required for anchoring acetylcholinesterase at the neuromuscular junction. PG - 505-15 AB - At the neuromuscular junction, acetylcholinesterase (AChE) is mainly present as asymmetric forms in which tetramers of catalytic subunits are associated to a specific collagen, collagen Q (ColQ). The accumulation of the enzyme in the synaptic basal lamina strictly relies on ColQ. This has been shown to be mediated by interaction between ColQ and perlecan, which itself binds dystroglycan. Here, using transfected mutants of ColQ in a ColQ-deficient muscle cell line or COS-7 cells, we report that ColQ clusterizes through a more complex mechanism. This process requires two heparin-binding sites contained in the collagen domain as well as the COOH terminus of ColQ. Cross-linking and immunoprecipitation experiments in Torpedo postsynaptic membranes together with transfection experiments with muscle-specific kinase (MuSK) constructs in MuSK-deficient myotubes or COS-7 cells provide the first evidence that ColQ binds MuSK. Together, our data suggest that a ternary complex containing ColQ, perlecan, and MuSK is required for AChE clustering and support the notion that MuSK dictates AChE synaptic localization at the neuromuscular junction. FAU - Cartaud, Annie AU - Cartaud A AD - Biologie Cellulaire des Membranes, Institut Jacques Monod, UMR 7592 Centre National de la Recherche Scientifique (CNRS), Universites Paris 6 and Paris 7, 75251 Paris, Cedex 05, France. FAU - Strochlic, Laure AU - Strochlic L FAU - Guerra, Manuel AU - Guerra M FAU - Blanchard, Benoit AU - Blanchard B FAU - Lambergeon, Monique AU - Lambergeon M FAU - Krejci, Eric AU - Krejci E FAU - Cartaud, Jean AU - Cartaud J FAU - Legay, Claire AU - Legay C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Heparan Sulfate Proteoglycans) RN - 0 (Macromolecular Substances) RN - 0 (Muscle Proteins) RN - 0 (Receptors, Cholinergic) RN - 143972-95-6 (perlecan) RN - 9007-34-5 (Collagen) RN - EC 2.7.10.1 (MUSK protein, human) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 3.1.1.7 (Acetylcholinesterase) RN - EC 3.1.1.7 (COLQ protein, human) SB - IM MH - Acetylcholinesterase/genetics/*metabolism MH - Animals MH - Binding Sites/genetics MH - COS Cells MH - Collagen/genetics/metabolism MH - Heparan Sulfate Proteoglycans/metabolism MH - Macromolecular Substances MH - Mice MH - Mice, Knockout MH - Muscle Fibers, Skeletal/cytology/enzymology MH - Muscle Proteins/genetics/metabolism MH - Mutation/genetics MH - Neuromuscular Junction/*enzymology/ultrastructure MH - Protein Binding/genetics MH - Receptor Aggregation/genetics MH - Receptor Protein-Tyrosine Kinases/*metabolism MH - Receptors, Cholinergic/*metabolism MH - Synaptic Membranes/*enzymology/ultrastructure MH - Synaptic Transmission/genetics MH - Transfection PMC - PMC2172359 EDAT- 2004/05/26 05:00 MHDA- 2004/09/10 05:00 PMCR- 2004/11/24 CRDT- 2004/05/26 05:00 PHST- 2004/05/26 05:00 [pubmed] PHST- 2004/09/10 05:00 [medline] PHST- 2004/05/26 05:00 [entrez] PHST- 2004/11/24 00:00 [pmc-release] AID - jcb.200307164 [pii] AID - 200307164 [pii] AID - 10.1083/jcb.200307164 [doi] PST - ppublish SO - J Cell Biol. 2004 May 24;165(4):505-15. doi: 10.1083/jcb.200307164.