Dataset Information


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

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 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.

SUBMITTER: Nakamura Y 

PROVIDER: S-EPMC3041953 | BioStudies | 2011-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2013-01-01 | S-EPMC3725416 | BioStudies
1000-01-01 | S-EPMC2414292 | BioStudies
2008-01-01 | S-EPMC2664613 | BioStudies
1000-01-01 | S-EPMC4282554 | BioStudies
2014-01-01 | S-EPMC3951436 | BioStudies
1000-01-01 | S-EPMC6168463 | BioStudies
1000-01-01 | S-EPMC3003028 | BioStudies
2020-01-01 | S-EPMC7449969 | BioStudies
2018-01-01 | S-EPMC6128908 | BioStudies
1000-01-01 | S-EPMC2672538 | BioStudies