role of myosin va in the plasticity of the vertebrate neuromuscular junction in vivo肌凝蛋白va在脊椎动物体内神经肌肉接点的可塑性.pdfVIP

Role of Myosin Va in the Plasticity of the Vertebrate Neuromuscular Junction In Vivo ¨ 1 1 1 2 3 Ira Verena Roder , Yvonne Petersen , Kyeong Rok Choi , Veit Witzemann , John A. Hammer, III , ¨ 1* Rudiger Rudolf 1 Institute of Toxicology and Genetics, Research Center Karlsruhe, Eggenstein-Leopoldshafen, Germany, 2 Max-Planck-Institute for Medical Research, Heidelberg, Germany, 3 Laboratory of Cell Biology, National Institutes of Health, Bethesda, Maryland, United States of America Abstract Background: Myosin Va is a motor protein involved in vesicular transport and its absence leads to movement disorders in humans (Griscelli and Elejalde syndromes) and rodents (e.g. dilute lethal phenotype in mice). We examined the role of myosin Va in the postsynaptic plasticity of the vertebrate neuromuscular junction (NMJ). Methodology/Principal Findings: Dilute lethal mice showed a good correlation between the propensity for seizures, and fragmentation and size reduction of NMJs. In an aneural C2C12 myoblast cell culture, expression of a dominant-negative fragment of myosin Va led to the accumulation of punctate structures containing the NMJ marker protein, rapsyn-GFP, in perinuclear clusters. In mouse hindlimb muscle, endogenous myosin Va co-precipitated with surface-exposed or internalised acetylcholine receptors and was markedly enriched in close proximity to the NMJ upon immunofluorescence. In vivo microscopy of exogenous full length myosin Va as well as a cargo-binding fragment of myosin Va showed localisation to the NMJ in wildtype mouse muscles. Furthermore, local interference with myosin Va function in live wildtype mouse muscles led to fragmentation and