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

doi:10.1016/j.neuron.2013.05.003

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 journal › Article (Academic Journal) › peer-review

77 Citations (Scopus)

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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 language	English
Pages (from-to)	293-307
Number of pages	15
Journal	Neuron
Volume	79
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2013.05.003
Publication status	Published - 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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10.1016/j.neuron.2013.05.003

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PICK1 links AMPA receptor stimulation to Cdc42
Rocca, D. & Hanley, J., 12 Jan 2015, In: Neuroscience Letters. 585, p. 155-159 5 p.
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Actin-dependent mechanisms in AMPA receptor trafficking.
Hanley, J., 12 Nov 2014, In: Frontiers in Cellular Neuroscience. 8, 381.
Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Subunit-specific trafficking mechanisms regulating the synaptic expression of Ca²⁺-permeable AMPA receptors.
Hanley, J., Mar 2014, In: Seminars in Cell and Developmental Biology. 27, p. 14–22 9 p.
Research output: Contribution to journal › Article (Academic Journal) › peer-review

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BBSRC - link account to BIOC RA0514 (BB/H014284/1): 'Regulation of Arp2/3-mediated actin polymerisation by PICK1 in neuronal function'.
Mellor, J. R. (Principal Investigator)
10/01/11 → 10/01/14
Project: Research
Regulation of Arp2/3-mediated actin polymerisation by PICK1 in neuronal function.
Hanley, J. G. (Principal Investigator)
10/01/11 → 10/06/14
Project: Research
MECHANISMS OF NMDA RECEPTOR DEPENDANT LTP AND LTD IN THE HIPPOCAMPUS
Collingridge, G. L. (Principal Investigator)
1/01/08 → 1/04/13
Project: Research

Cite this

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

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.",

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author = "Rocca, \{Daniel L\} and Mascia Amici and Anna Antoniou and \{Blanco Suarez\}, Elena and Nagaraj Halemani and Kai Murk and Jennifer McGarvey and Nadia Jaafari and Mellor, \{Jack R\} and Collingridge, \{Graham L\} and Hanley, \{Jonathan G\}",

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AU - Rocca, Daniel L

AU - Amici, Mascia

AU - Antoniou, Anna

AU - Blanco Suarez, Elena

AU - Halemani, Nagaraj

AU - Murk, Kai

AU - McGarvey, Jennifer

AU - Jaafari, Nadia

AU - Mellor, Jack R

AU - Collingridge, Graham L

AU - Hanley, Jonathan G

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N2 - 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.

AB - 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.

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KW - Actin-Related Protein 2-3 Complex

KW - Actins

KW - Animals

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KW - Carrier Proteins

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KW - Cercopithecus aethiops

KW - HEK293 Cells

KW - Humans

KW - Neuronal Plasticity

KW - Nuclear Proteins

KW - Organ Culture Techniques

KW - Polymerization

KW - Rats

KW - Rats, Wistar

KW - Synapses

U2 - 10.1016/j.neuron.2013.05.003

DO - 10.1016/j.neuron.2013.05.003

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AN - SCOPUS:84880680169

SN - 0896-6273

VL - 79

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JO - Neuron

JF - Neuron

IS - 2

ER -

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

Abstract

Keywords

Access to Document

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Research output

PICK1 links AMPA receptor stimulation to Cdc42

Actin-dependent mechanisms in AMPA receptor trafficking.

Subunit-specific trafficking mechanisms regulating the synaptic expression of Ca2+-permeable AMPA receptors.

Projects

BBSRC - link account to BIOC RA0514 (BB/H014284/1): 'Regulation of Arp2/3-mediated actin polymerisation by PICK1 in neuronal function'.

Regulation of Arp2/3-mediated actin polymerisation by PICK1 in neuronal function.

MECHANISMS OF NMDA RECEPTOR DEPENDANT LTP AND LTD IN THE HIPPOCAMPUS

Cite this

Subunit-specific trafficking mechanisms regulating the synaptic expression of Ca²⁺-permeable AMPA receptors.