<p>Membrane trafficking in dendritic spines is critical for regulating the number of channels and spine structure during synaptic plasticity. Here I report two small Rab GTPases, Rab4 and Rab10, oppositely regulate AMPA receptors (AMPARs) trafficking and structural plasticity of dendritic spines. Combining two-photon glutamate uncaging with two-photon fluorescence lifetime imaging microscopy (2pFLIM), I found that Rab4 is transiently activated whereas Rab10 is persistently inactivated in the stimulated spines during structural long-term potentiation (sLTP). Inhibition of Rab4 signaling has no effect on GluA1 endocytosis but inhibits activity-dependent GluA1 exocytosis. Conversely, disruption of Rab10 signaling inhibits GluA1 endocytosis while enhancing activity-dependent GluA1 exocytosis. In summary, these results uncover a new mechanism to establish the specificity and directionality of AMPARs trafficking and sLTP via distinct regulations of Rab4 and Rab10 signaling.</p> / Dissertation
| Identifer | oai:union.ndltd.org:DUKE/oai:dukespace.lib.duke.edu:10161/13379 |
| Date | January 2016 |
| Creators | Wang, Jie |
| Contributors | Yasuda, Ryohei |
| Source Sets | Duke University |
| Detected Language | English |
| Type | Dissertation |
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