Journal
JOURNAL OF CELL BIOLOGY
Volume 168, Issue 2, Pages 329-338Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200410091
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Funding
- NIDDK NIH HHS [DK 25387, R37 DK025387, R56 DK025387, P01-DK55389, P01 DK055389, R01 DK025387] Funding Source: Medline
- NINDS NIH HHS [NS66274-01, K12 NS066274] Funding Source: Medline
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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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