期刊
EMBO JOURNAL
卷 30, 期 4, 页码 719-730出版社
WILEY
DOI: 10.1038/emboj.2010.357
关键词
actin; AMPA receptor; cytoskeleton; dendritic spine; synapse
资金
- MRC
- Wellcome Trust
- ENI-NET
- Engineering and Physical Sciences Research Council [EP/E500110/1] Funding Source: researchfish
- Medical Research Council [G0601841B, G0601810] Funding Source: researchfish
- MRC [G0601810] Funding Source: UKRI
Activity-dependent remodelling of dendritic spines is essential for neural circuit development and synaptic plasticity, but the precise molecular mechanisms that regulate this process are unclear. Activators of Arp2/3-mediated actin polymerisation are required for spine enlargement; however, during long-term depression (LTD), spines shrink via actin depolymerisation and Arp2/3 inhibitors in this process have not yet been identified. Here, we show that PICK1 regulates spine size in hippocampal neurons via inhibition of the Arp2/3 complex. PICK1 knockdown increases spine size, whereas PICK1 overexpression reduces spine size. NMDA receptor activation results in spine shrinkage, which is blocked by PICK1 knockdown or overexpression of a PICK1 mutant that cannot bind Arp2/3. Furthermore, we show that PICK1-Arp2/3 interactions are required for functional hippocampal LTD. This work demonstrates that PICK1 is a novel regulator of spine dynamics. Via Arp2/3 inhibition, PICK1 has complementary yet distinct roles during LTD to regulate AMPA receptor trafficking and spine size, and therefore functions as a crucial factor in both structural and functional plasticity. The EMBO Journal (2011) 30, 719-730. doi:10.1038/emboj.2010.357; Published online 21 January 2011
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