RGD Reference Report - The small GTPase Arf1 modulates Arp2/3-mediated actin polymerization via PICK1 to regulate synaptic plasticity. - Rat Genome Database

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The small GTPase Arf1 modulates Arp2/3-mediated actin polymerization via PICK1 to regulate synaptic plasticity.

Authors: Rocca, DL  Amici, M  Antoniou, A  Blanco Suarez, E  Halemani, N  Murk, K  McGarvey, J  Jaafari, N  Mellor, JR  Collingridge, GL  Hanley, JG 
Citation: Rocca DL, etal., Neuron. 2013 Jul 24;79(2):293-307. doi: 10.1016/j.neuron.2013.05.003.
RGD ID: 8553918
Pubmed: (View Article at PubMed) PMID:23889934
DOI: Full-text: DOI:10.1016/j.neuron.2013.05.003

Inhibition of Arp2/3-mediated actin polymerization by PICK1 is a central mechanism to AMPA receptor (AMPAR) internalization and long-term depression (LTD), although the signaling pathways that modulate this process in response to NMDA receptor (NMDAR) activation are unknown. Here, we define a function for the GTPase Arf1 in this process. We show that Arf1-GTP binds PICK1 to limit PICK1-mediated inhibition of Arp2/3 activity. Expression of mutant Arf1 that does not bind PICK1 leads to reduced surface levels of GluA2-containing AMPARs and smaller spines in hippocampal neurons, which occludes subsequent NMDA-induced AMPAR internalization and spine shrinkage. In organotypic slices, NMDAR-dependent LTD of AMPAR excitatory postsynaptic currents is abolished in neurons expressing mutant Arf1. Furthermore, NMDAR stimulation downregulates Arf1 activation and binding to PICK1 via the Arf-GAP GIT1. This study defines Arf1 as a critical regulator of actin dynamics and synaptic function via modulation of PICK1.

Annotation

Gene Ontology Annotations    

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Arf1  (ADP-ribosylation factor 1)
Pick1  (protein interacting with PRKCA 1)


Additional Information