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Publication : A role for myosin VI in postsynaptic structure and glutamate receptor endocytosis.

First Author  Osterweil E Year  2005
Journal  J Cell Biol Volume  168
Issue  2 Pages  329-38
PubMed ID  15657400 Mgi Jnum  J:95877
Mgi Id  MGI:3527915 Doi  10.1083/jcb.200410091
Citation  Osterweil E, et al. (2005) A role for myosin VI in postsynaptic structure and glutamate receptor endocytosis. J Cell Biol 168(2):329-38
abstractText  Myosin VI (Myo6) is an actin-based motor protein implicated in clathrin-mediated endocytosis in nonneuronal cells, though little is known about its function in the nervous system. Here, we find that Myo6 is highly expressed throughout the brain, localized to synapses, and enriched at the postsynaptic density. Myo6-deficient (Snell's waltzer; sv/sv) hippocampus exhibits a decrease in synapse number, abnormally short dendritic spines, and profound astrogliosis. Similarly, cultured sv/sv hippocampal neurons display decreased numbers of synapses and dendritic spines, and dominant-negative disruption of Myo6 in wild-type hippocampal neurons induces synapse loss. Importantly, we find that sv/sv hippocampal neurons display a significant deficit in the stimulation-induced internalization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptors (AMPARs), and that Myo6 exists in a complex with the AMPAR, AP-2, and SAP97 in brain. These results suggest that Myo6 plays a role in the clathrin-mediated endocytosis of AMPARs, and that its loss leads to alterations in synaptic structure and astrogliosis.
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