PICK1 inhibition of the Arp2/3 complex controls dendritic spine size and synaptic plasticity

Yasuko Nakamura, C.L Wood, A.P Patton, N Jaafari, J.M Henley, J.R Mellor, J.G Hanley

Research output: Contribution to journalArticle (Academic Journal)peer-review

75 Citations (Scopus)

Abstract

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 olymerisation 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.
Translated title of the contributionPICK1 inhibition of the Arp2/3 complex controls dendritic spine size and synaptic plasticity
Original languageEnglish
Pages (from-to)719 - 730
Number of pages12
JournalEMBO Journal
Volume30
Issue number4
DOIs
Publication statusPublished - Feb 2011

Bibliographical note

Other: EMBO open

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    Ulcigrai, C.

    1/08/071/08/12

    Project: Research

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