The Small GTPase Arf1 Modulates Arp2/3-Mediated Actin Polymerization via PICK1 to Regulate Synaptic Plasticity

Daniel L Rocca, Mascia Amici, Anna Antoniou, Elena Blanco Suarez, Nagaraj Halemani, Kai Murk, Jennifer McGarvey, Nadia Jaafari, Jack R Mellor, Graham L Collingridge, Jonathan G Hanley

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

61 Citations (Scopus)
736 Downloads (Pure)

Abstract

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.
Original languageEnglish
Pages (from-to)293-307
Number of pages15
JournalNeuron
Volume79
Issue number2
DOIs
Publication statusPublished - 24 Jul 2013

Keywords

  • ADP-Ribosylation Factor 1
  • Actin-Related Protein 2-3 Complex
  • Actins
  • Animals
  • COS Cells
  • Carrier Proteins
  • Cells, Cultured
  • Cercopithecus aethiops
  • HEK293 Cells
  • Humans
  • Neuronal Plasticity
  • Nuclear Proteins
  • Organ Culture Techniques
  • Polymerization
  • Rats
  • Rats, Wistar
  • Synapses

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