The Small GTPase Arf1 Modulates Arp2/3-Mediated Actin Polymerization via PICK1 to Regulate Synaptic Plasticity
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
LifeactGFP FRAP confirms increased actin recovery in Cyfip1+/− neurons.
“Similar results were also obtained using LifeactGFP, an F-actin-specific fluorescent probe suitable for FRAP experiments.42 Photobleaching spines expressing LifeactGFP produced a significantly greater amount of recovered fluorescence in Cyfip1+/− neurons compared with WT again by 40 s (WT: 67.9±4.8%, Cyfip1+/−: 85.5±7.0%, P<0.05; Figure 4d) resulting in a significant increase in the total mobile”
From The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines (2014) · cites this paper as [42]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Long-term depression in the CNS
Collingridge, G. L., Peineau, S., Howland, J. G., & Wang, Y. T. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2867 · Cited by 926 · see citing works
Self-citationRegulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD
Beattie, E. C., Carroll, R. C., Yu, X., Morishita, W., Yasuda, H., von Zastrow, M., & Malenka, R. C. (2000) · Nature Neuroscience · doi:10.1038/81823 · Cited by 745 · see citing works
Steinberg, J. P., Takamiya, K., Shen, Y., Xia, J., Rubio, M. E., Yu, S., Jin, W., Thomas, G. M., Linden, D. J., & Huganir, R. L. (2006) · Neuron · doi:10.1016/j.neuron.2006.02.025 · Cited by 288 · cited 1× · see citing works
“PICK1-mediated GluA2 trafficking is also a crucial mechanism in cerebellar LTD (Steinberg et al., 2006; Xia et al., 2000), indicating the central importance of PICK1 in synaptic plasticity.”
PICK1 inhibition of the Arp2/3 complex controls dendritic spine size and synaptic plasticity
Nakamura, Y., Wood, C. L., Patton, A. P., Jaafari, N., Henley, J. M., Mellor, J. R., & Hanley, J. G. (2011) · The EMBO Journal · doi:10.1038/emboj.2010.357 · Cited by 97 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 42
- Anderson W.W. Collingridge G.L. Capabilities of the WinLTP data acquisition program extending beyond basic LTP experimental functions J. Neurosci. Methods 162 2007 346 356 17306885
- Ashby M.C. De La Rue S.A. Ralph G.S. Uney J. Collingridge G.L. Henley J.M. Removal of AMPA receptors (AMPARs) from synapses is preceded by transient endocytosis of extrasynaptic AMPARs J. Neurosci. 24 2004 5172 5176 15175386 PMC3309030
- Bassani S. Cingolani L.A. Valnegri P. Folci A. Zapata J. Gianfelice A. Sala C. Goda Y. Passafaro M. The X-linked intellectual disability protein TSPAN7 regulates excitatory synapse development and AMPAR trafficking Neuron 73 2012 1143 1158 22445342 PMC3314997
- Bortolotto Z.A. Amici M. Anderson W.W. Isaac J.T. Collingridge G.L. Synaptic plasticity in the hippocampal slice preparation Curr. Protoc. Neurosci. Chapter 6 2011 Unit 6.13 21207366
- Cingolani L.A. Goda Y. Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy Nat. Rev. Neurosci. 9 2008 344 356 18425089
- Citri A. Bhattacharyya S. Ma C. Morishita W. Fang S. Rizo J. Malenka R.C. Calcium binding to PICK1 is essential for the intracellular retention of AMPA receptors underlying long-term depression J. Neurosci. 30 2010 16437 16452 21147983 PMC3004477
- D’Souza-Schorey C. Chavrier P. ARF proteins: roles in membrane traffic and beyond Nat. Rev. Mol. Cell Biol. 7 2006 347 358 16633337
- Dascher C. Balch W.E. Dominant inhibitory mutants of ARF1 block endoplasmic reticulum to Golgi transport and trigger disassembly of the Golgi apparatus J. Biol. Chem. 269 1994 1437 1448 8288610
- Dubois T. Paléotti O. Mironov A.A. Fraisier V. Stradal T.E. De Matteis M.A. Franco M. Chavrier P. Golgi-localized GAP for Cdc42 functions downstream of ARF1 to control Arp2/3 complex and F-actin dynamics Nat. Cell Biol. 7 2005 353 364 15793564
- Gillingham A.K. Munro S. The small G proteins of the Arf family and their regulators Annu. Rev. Cell Dev. Biol. 23 2007 579 611 17506703
- Hanley J.G. PICK1: a multi-talented modulator of AMPA receptor trafficking Pharmacol. Ther. 118 2008 152 160 18353440
- Hanley J.G. Henley J.M. PICK1 is a calcium-sensor for NMDA-induced AMPA receptor trafficking EMBO J. 24 2005 3266 3278 16138078 PMC1224691
- Harris B.Z. Lim W.A. Mechanism and role of PDZ domains in signaling complex assembly J. Cell Sci. 114 2001 3219 3231 11591811
- Heuvingh J. Franco M. Chavrier P. Sykes C. ARF1-mediated actin polymerization produces movement of artificial vesicles Proc. Natl. Acad. Sci. USA 104 2007 16928 16933 17942688 PMC2040406
- Hotulainen P. Hoogenraad C.C. Actin in dendritic spines: connecting dynamics to function J. Cell Biol. 189 2010 619 629 20457765 PMC2872912
- Hotulainen P. Llano O. Smirnov S. Tanhuanpää K. Faix J. Rivera C. Lappalainen P. Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis J. Cell Biol. 185 2009 323 339 19380880 PMC2700375
- Kaksonen M. Toret C.P. Drubin D.G. Harnessing actin dynamics for clathrin-mediated endocytosis Nat. Rev. Mol. Cell Biol. 7 2006 404 414 16723976
- Klockenbusch C. Kast J. Optimization of formaldehyde cross-linking for protein interaction analysis of non-tagged integrin beta1 J. Biomed. Biotechnol. 2010 2010 927585 20634879 PMC2896913
- Ko J. Kim S. Valtschanoff J.G. Shin H. Lee J.R. Sheng M. Premont R.T. Weinberg R.J. Kim E. Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting J. Neurosci. 23 2003 1667 1677 12629171 PMC6741975
- Lu W. Ziff E.B. PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking Neuron 47 2005 407 421 16055064
- Merrifield C.J. Seeing is believing: imaging actin dynamics at single sites of endocytosis Trends Cell Biol. 14 2004 352 358 15246428
- Myers K.R. Casanova J.E. Regulation of actin cytoskeleton dynamics by Arf-family GTPases Trends Cell Biol. 18 2008 184 192 18328709 PMC2885709
- Nie Z. Hirsch D.S. Randazzo P.A. Arf and its many interactors Curr. Opin. Cell Biol. 15 2003 396 404 12892779
- Palmer M.J. Irving A.J. Seabrook G.R. Jane D.E. Collingridge G.L. The group I mGlu receptor agonist DHPG induces a novel form of LTD in the CA1 region of the hippocampus Neuropharmacology 36 1997 1517 1532 9517422
- Pollard T.D. Regulation of actin filament assembly by Arp2/3 complex and formins Annu. Rev. Biophys. Biomol. Struct. 36 2007 451 477 17477841
- Rocca D.L. Martin S. Jenkins E.L. Hanley J.G. Inhibition of Arp2/3-mediated actin polymerization by PICK1 regulates neuronal morphology and AMPA receptor endocytosis Nat. Cell Biol. 10 2008 259 271 18297063 PMC2664613
- Scholz R. Berberich S. Rathgeber L. Kolleker A. Köhr G. Kornau H.C. AMPA receptor signaling through BRAG2 and Arf6 critical for long-term synaptic depression Neuron 66 2010 768 780 20547133
- Shepherd J.D. Huganir R.L. The cell biology of synaptic plasticity: AMPA receptor trafficking Annu. Rev. Cell Dev. Biol. 23 2007 613 643 17506699
- Sossa K.G. Court B.L. Carroll R.C. NMDA receptors mediate calcium-dependent, bidirectional changes in dendritic PICK1 clustering Mol. Cell. Neurosci. 31 2006 574 585 16406232
- Star E.N. Kwiatkowski D.J. Murthy V.N. Rapid turnover of actin in dendritic spines and its regulation by activity Nat. Neurosci. 5 2002 239 246 11850630
- Stoppini L. Buchs P.A. Muller D. A simple method for organotypic cultures of nervous tissue J. Neurosci. Methods 37 1991 173 182 1715499
- Stradal T.E. Scita G. Protein complexes regulating Arp2/3-mediated actin assembly Curr. Opin. Cell Biol. 18 2006 4 10 16343889
- Takenawa T. Suetsugu S. The WASP-WAVE protein network: connecting the membrane to the cytoskeleton Nat. Rev. Mol. Cell Biol. 8 2007 37 48 17183359
- Takeya R. Takeshige K. Sumimoto H. Interaction of the PDZ domain of human PICK1 with class I ADP-ribosylation factors Biochem. Biophys. Res. Commun. 267 2000 149 155 10623590
- Terashima A. Pelkey K.A. Rah J.C. Suh Y.H. Roche K.W. Collingridge G.L. McBain C.J. Isaac J.T. An essential role for PICK1 in NMDA receptor-dependent bidirectional synaptic plasticity Neuron 57 2008 872 882 18367088 PMC2336895
- Terashima A. Cotton L. Dev K.K. Meyer G. Zaman S. Duprat F. Henley J.M. Collingridge G.L. Isaac J.T. Regulation of synaptic strength and AMPA receptor subunit composition by PICK1 J. Neurosci. 24 2004 5381 5390 15190111 PMC3310907
- Volk L. Kim C.H. Takamiya K. Yu Y. Huganir R.L. Developmental regulation of protein interacting with C kinase 1 (PICK1) function in hippocampal synaptic plasticity and learning Proc. Natl. Acad. Sci. USA 107 2010 21784 21789 21106762 PMC3003028
- Volpicelli-Daley L.A. Li Y. Zhang C.J. Kahn R.A. Isoform-selective effects of the depletion of ADP-ribosylation factors 1-5 on membrane traffic Mol. Biol. Cell 16 2005 4495 4508 16030262 PMC1237059
- Xia J. Zhang X. Staudinger J. Huganir R.L. Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1 Neuron 22 1999 179 187 10027300
- Xia J. Chung H.J. Wihler C. Huganir R.L. Linden D.J. Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins Neuron 28 2000 499 510 11144359
- Xu J. Xia J. Structure and function of PICK1 Neurosignals 15 2006–2007 190 201 17215589
- Zhang H. Webb D.J. Asmussen H. Horwitz A.F. Synapse formation is regulated by the signaling adaptor GIT1 J. Cell Biol. 161 2003 131 142 12695502 PMC2172873
Cited by
Sorted by citations
AMPARs and Synaptic Plasticity: The Last 25 Years
Huganir, R. L., & Nicoll, R. A. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.025 · Cited by 968 · see citing works
Pathania, M., Davenport, E. C., Muir, J., Sheehan, D. F., López-Doménech, G., & Kittler, J. T. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.16 · Cited by 189 · see citing works
Davenport, E. C., Szulc, B. R., Drew, J., Taylor, J., Morgan, T., Higgs, N. F., López-Doménech, G., & Kittler, J. T. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.092 · Cited by 125 · see citing works
Synapse rearrangements upon learning: from divergent–sparse connectivity to dedicated sub-circuits
Caroni, P., Chowdhury, A., & Lahr, M. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.08.011 · Cited by 85 · see citing works
- Authors
- Rocca, D. L., Amici, M., Antoniou, A., Blanco Suarez, E., Halemani, N., Murk, K., McGarvey, J., Jaafari, N., Mellor, J. R., Collingridge, G. L., & Hanley, J. G.
- Affiliations
- University of Bristol (GB)
- Seoul National University (KR)
- Corresponding author
- Hanley, Jonathan G.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 79
- Issue
- 2
- Pages
- 293-307
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3725416
- OpenAlex
- W2120820768
- Cited by
- 90
- References
- 4
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 12 · 2017: 9 · 2016: 15 · 2015: 8 · 2014: 12 · 2013: 1
- FWCI
- 5.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Explore Bristol Research (submittedVersion, cc-by)
- Funders
- Wellcome Trust (089703)
- National Institutes of Health
- Medical Research Council (MC_G1000734)
- Engineering and Physical Sciences Research Council (EP/E500110/1)
- Biotechnology and Biological Sciences Research Council (BB/H014284/1)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Arf1, PICK1, Arp2/3 complex, actin polymerization, synaptic plasticity, long-term depression, AMPA receptor internalization, GluA2, NMDA receptor, GIT1, ArfGAP, dendritic spines, hippocampal neurons, actin dynamics
- MeSH terms
- Actins, Animals, Carrier Proteins, Cells, Cultured, Chlorocebus aethiops, Cytoskeletal Proteins, Humans, Neuronal Plasticity, Nuclear Proteins, Organ Culture Techniques, Synapses, Rats, Wistar, COS Cells, ADP-Ribosylation Factor 1, Actin-Related Protein 2-3 Complex, Rats, HEK293 Cells, Polymerization
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
