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标题：PKCγ-induced trafficking of AMPA receptors in embryonic zebrafish depends on NSF and PICK1
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作者：Shunmoogum A. Patten ; Declan W. Ali
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：16
页码：6796-6801
DOI：10.1073/pnas.0811171106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The trafficking of AMPA receptors (Rs) to and from synaptic membranes is a key component underlying synaptic plasticity mechanisms such as long-term potentiation (LTP) and long-term depression (LTD), and is likely important for synaptic development in embryonic organisms. However, some of the key biochemical components required for receptor trafficking in embryos are still unknown. Here, we report that in embryonic zebrafish, the activation of PKC{gamma} by phorbol 12-myristate 13-acetate, strongly potentiates the amplitude of AMPAR-mediated miniature excitatory postsynaptic currents (AMPA-mEPSCs) via a N-ethylmaleimide-sensitive fusion (NSF) and protein interacting with C-kinase-1 (PICK1)-dependent process. We found that the mEPSC potentiation is DAG- and Ca2+-dependent, and occurs on application of active PKC{gamma}. Peptides that prevent the association of NSF and PICK1 with the GluR2 subunit, and the actin-polymerization blocker, latrunculin B, prevented the increase in mEPSC amplitude. Also, application of tetanus toxin (TeTx), which cleaves SNARE proteins, also blocked the increase in mEPSC amplitude. Last, application of a 5 mM K+ medium led to an enhancement in mEPSC amplitude that was prevented by addition of the PKC{gamma} and NSF-blocking peptides, and the NMDA receptor blocker, 2-amino-5-phosphonovaleric acid (APV). Thus, activation of PKC{gamma} is necessary for the activity-dependent trafficking of AMPARs in embryonic zebrafish. This process is NMDA and SNARE-dependent and requires AMPARs to associate with both NSF and PICK1. The present data further our understanding of AMPAR trafficking, and have important implications for synaptic development and synaptic plasticity.
关键词：Mauthner neuron ; glutamate ; NMDA ; synapse ; development