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

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2013 Jul 30

PMID 23889934

Citations 54

Authors

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

Affiliations

Soon will be listed here.

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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References

Volk L, Kim C, Takamiya K, Yu Y, Huganir R . Developmental regulation of protein interacting with C kinase 1 (PICK1) function in hippocampal synaptic plasticity and learning. Proc Natl Acad Sci U S A. 2010; 107(50):21784-9. PMC: 3003028. DOI: 10.1073/pnas.1016103107. View

Scholz R, Berberich S, Rathgeber L, Kolleker A, Kohr G, Kornau H . AMPA receptor signaling through BRAG2 and Arf6 critical for long-term synaptic depression. Neuron. 2010; 66(5):768-80. DOI: 10.1016/j.neuron.2010.05.003. View

Nakamura Y, Wood C, Patton A, Jaafari N, Henley J, Mellor J . PICK1 inhibition of the Arp2/3 complex controls dendritic spine size and synaptic plasticity. EMBO J. 2011; 30(4):719-30. PMC: 3041953. DOI: 10.1038/emboj.2010.357. View

Pollard T . Regulation of actin filament assembly by Arp2/3 complex and formins. Annu Rev Biophys Biomol Struct. 2007; 36:451-77. DOI: 10.1146/annurev.biophys.35.040405.101936. View

Kaksonen M, Toret C, Drubin D . Harnessing actin dynamics for clathrin-mediated endocytosis. Nat Rev Mol Cell Biol. 2006; 7(6):404-14. DOI: 10.1038/nrm1940. View

Beattie E, Carroll R, Yu X, Morishita W, Yasuda H, von Zastrow M . Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD. Nat Neurosci. 2000; 3(12):1291-300. DOI: 10.1038/81823. View

Terashima A, Pelkey K, Rah J, Suh Y, Roche K, Collingridge G . An essential role for PICK1 in NMDA receptor-dependent bidirectional synaptic plasticity. Neuron. 2008; 57(6):872-82. PMC: 2336895. DOI: 10.1016/j.neuron.2008.01.028. View

Merrifield C . Seeing is believing: imaging actin dynamics at single sites of endocytosis. Trends Cell Biol. 2004; 14(7):352-8. DOI: 10.1016/j.tcb.2004.05.008. View

DSouza-Schorey C, Chavrier P . ARF proteins: roles in membrane traffic and beyond. Nat Rev Mol Cell Biol. 2006; 7(5):347-58. DOI: 10.1038/nrm1910. View

10.

Ashby M, De La Rue S, Ralph G, Uney J, Collingridge G, Henley J . Removal of AMPA receptors (AMPARs) from synapses is preceded by transient endocytosis of extrasynaptic AMPARs. J Neurosci. 2004; 24(22):5172-6. PMC: 3309030. DOI: 10.1523/JNEUROSCI.1042-04.2004. View

11.

Heuvingh J, Franco M, Chavrier P, Sykes C . ARF1-mediated actin polymerization produces movement of artificial vesicles. Proc Natl Acad Sci U S A. 2007; 104(43):16928-33. PMC: 2040406. DOI: 10.1073/pnas.0704749104. View

12.

Hanley J, Henley J . PICK1 is a calcium-sensor for NMDA-induced AMPA receptor trafficking. EMBO J. 2005; 24(18):3266-78. PMC: 1224691. DOI: 10.1038/sj.emboj.7600801. View

13.

Bortolotto Z, Amici M, Anderson W, Isaac J, Collingridge G . Synaptic plasticity in the hippocampal slice preparation. Curr Protoc Neurosci. 2011; Chapter 6:Unit 6.13. DOI: 10.1002/0471142301.ns0613s54. View

14.

Hotulainen P, Llano O, Smirnov S, Tanhuanpaa K, Faix J, Rivera C . Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis. J Cell Biol. 2009; 185(2):323-39. PMC: 2700375. DOI: 10.1083/jcb.200809046. View

15.

Dubois T, Paleotti O, Mironov A, Fraisier V, Stradal T, De Matteis M . Golgi-localized GAP for Cdc42 functions downstream of ARF1 to control Arp2/3 complex and F-actin dynamics. Nat Cell Biol. 2005; 7(4):353-64. DOI: 10.1038/ncb1244. View

16.

Xia J, Chung H, Wihler C, Huganir R, Linden D . Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins. Neuron. 2001; 28(2):499-510. DOI: 10.1016/s0896-6273(00)00128-8. View

17.

Anderson W, Collingridge G . Capabilities of the WinLTP data acquisition program extending beyond basic LTP experimental functions. J Neurosci Methods. 2007; 162(1-2):346-56. DOI: 10.1016/j.jneumeth.2006.12.018. View

18.

Steinberg J, Takamiya K, Shen Y, Xia J, Rubio M, Yu S . Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression. Neuron. 2006; 49(6):845-60. DOI: 10.1016/j.neuron.2006.02.025. View

19.

Gillingham A, Munro S . The small G proteins of the Arf family and their regulators. Annu Rev Cell Dev Biol. 2007; 23:579-611. DOI: 10.1146/annurev.cellbio.23.090506.123209. View

20.

Stradal T, Scita G . Protein complexes regulating Arp2/3-mediated actin assembly. Curr Opin Cell Biol. 2005; 18(1):4-10. DOI: 10.1016/j.ceb.2005.12.003. View