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Disruption of the interaction between myosin VI and SAP97 is associated with a reduction in the number of AMPARs at hippocampal synapses
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Nash, Joanne E., Appleby, Vanessa J., Corrêa, Sônia A. L., Wu, Hongju, Fitzjohn, Stephen M., Garner, Craig C., Collingridge, Graham L. and Molnar, Elek. (2010) Disruption of the interaction between myosin VI and SAP97 is associated with a reduction in the number of AMPARs at hippocampal synapses. Journal of Neurochemistry, Vol.112 (No.3). pp. 677-690. ISSN 0022-3042
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Official URL: http://dx.doi.org/10.1111/j.1471-4159.2009.06480.x
Abstract
Myosin VI is an actin-based motor protein that is enriched at the postsynaptic density and appears to interact with alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptors (AMPARs) via synapse associated protein 97 (SAP97). Here, we find that a Flag epitope-tagged dominant negative construct that inhibits the interaction between SAP97 and myosin VI (Flag-myoVI-DN) causes a dramatic reduction in the number of synapses and the surface expression of AMPARs in cultured hippocampal neurons. Furthermore, we find that Flag-myoVI-DN also prevents the rapid delivery of AMPARs to synapses that can be induced by the transient activation of N-methyl-d-aspartate receptors. The Flag-myoVI-DN induced decrease in surface AMPARs is not because of reduced AMPAR subunit protein synthesis. Using whole-cell recording, we show that Flag-myoVI-DN also prevents the activity-induced increase in miniature excitatory postsynaptic current frequency that is normally associated with recruitment of AMPARs to the cell surface at synaptic sites that lack these receptors (i.e. 'silent' synapses). Together, these results indicate that myosin VI/SAP97 plays an important role in trafficking and activity-dependent recruitment of AMPARs to synapses.
| Item Type: | Journal Article |
|---|---|
| Subjects: | Q Science > Q Science (General) |
| Divisions: | Faculty of Science > Life Sciences (2010- ) |
| Journal or Publication Title: | Journal of Neurochemistry |
| Publisher: | Wiley-Blackwell Publishing Ltd. |
| ISSN: | 0022-3042 |
| Date: | 2010 |
| Volume: | Vol.112 |
| Number: | No.3 |
| Number of Pages: | 14 |
| Page Range: | pp. 677-690 |
| Identification Number: | 10.1111/j.1471-4159.2009.06480.x |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| Funder: | Medical Research Council (MRC) UK , Biotechnology and Biological Sciences Research Council (BBSRC) UK, Wellcome Trust, University of Warwick |
| Grant number: | 80049, 57294 (MRC), BB/F011326/1(BBSRU), 08141 (Warwick) |
| URI: | http://wrap.warwick.ac.uk/id/eprint/42512 |
Data sourced from Thomson Reuters' Web of Knowledge
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