Premium
PICK1 inhibition of the Arp2/3 complex controls dendritic spine size and synaptic plasticity
Author(s) -
Nakamura Yasuko,
Wood Catherine L,
Patton Andrew P,
Jaafari Nadia,
Henley Jeremy M,
Mellor Jack R,
Hanley Jonathan G
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.357
Subject(s) - dendritic spine , biology , synaptic plasticity , microbiology and biotechnology , actin remodeling of neurons , dendritic filopodia , neuroscience , gene knockdown , hippocampal formation , actin cytoskeleton , receptor , cytoskeleton , biochemistry , cell , apoptosis
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.