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Title

Local Control of AMPA Receptor Trafficking at the Postsynaptic Terminal by a Small GTPase of the Rab Family

AuthorsGerges, Nashaat Z.; Backos, D. S.; Esteban, José A.
KeywordsAMPA-type glutamatergic receptor
Red fluorescence protein
N-methyl-d-aspartate receptor
Issue Date15-Oct-2004
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationJournal of Biological Chemistry 279: 43870-43878 (2004)
AbstractThe delivery of neurotransmitter receptors into the synaptic membrane is essential for synaptic function and plasticity. However, the molecular mechanisms of these specialized trafficking events and their integration with the intracellular membrane transport machinery are virtually unknown. Here, we have investigated the role of the Rab family of membrane sorting proteins in the late stages of receptor trafficking into the postsynaptic membrane. We have identified Rab8, a vesicular transport protein associated with trans-Golgi network membranes, as a critical component of the cellular machinery that delivers AMPA-type glutamatergic receptors (AMPARs) into synapses. Using electron microscopic techniques, we have found that Rab8 is localized in close proximity to the synaptic membrane, including the postsynaptic density. Electrophysiological studies indicated that Rab8 is necessary for the synaptic delivery of AMPARs during plasticity (long-term potentiation) and during constitutive receptor cycling. In addition, Rab8 is required for AMPAR delivery into the spine surface, but not for receptor transport from the dendritic shaft into the spine compartment or for delivery into the dendritic surface. Therefore, Rab8 specifically drives the local delivery of AMPARs into synapses. These results demonstrate a new role for the cellular secretory machinery in the control of synaptic function and plasticity directly at the postsynaptic membrane.
Publisher version (URL)http://dx.doi.org/10.1074/jbc.M404982200
URIhttp://hdl.handle.net/10261/37620
DOI10.1074/jbc.M404982200
ISSN0021-9258
Appears in Collections:(CBM) Artículos
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