Cited by 97Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersMemory and Neural Mechanisms

PICK1 inhibition of the Arp2/3 complex controls dendritic spine size and synaptic plasticity

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Nakamura, Yasuko, Wood, Catherine L, Patton, Andrew P, Jaafari, Nadia, Henley, Jeremy M, Mellor, Jack R, Hanley, Jonathan G·2011·The EMBO Journal

Abstract

Activity-dependent remodelling of dendritic spines is essential for neural circuit development and synaptic plasticity, but the precise molecular mechanisms that regulate this process are unclear. Activators of Arp2/3-mediated actin polymerisation are required for spine enlargement; however, during long-term depression (LTD), spines shrink via actin depolymerisation and Arp2/3 inhibitors in this process have not yet been identified. Here, we show that PICK1 regulates spine size in hippocampal neurons via inhibition of the Arp2/3 complex. PICK1 knockdown increases spine size, whereas PICK1 overexpression reduces spine size. NMDA receptor activation results in spine shrinkage, which is blocked by PICK1 knockdown or overexpression of a PICK1 mutant that cannot bind Arp2/3. Furthermore, we show that PICK1-Arp2/3 interactions are required for functional hippocampal LTD. This work demonstrates that PICK1 is a novel regulator of spine dynamics. Via Arp2/3 inhibition, PICK1 has complementary yet distinct roles during LTD to regulate AMPA receptor trafficking and spine size, and therefore functions as a crucial factor in both structural and functional plasticity.

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Crossref · 10.1038/emboj.2010.357

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  • Brief bath application of 20 μM NMDA plus 20 μM glycine induces a 15-20% spine shrinkage within 40 min, measured as a decrease in spine volume without a concomitant change in spine diameter or length.

    “Brief bath application of 20 μM NMDA plus 20 μM glycine induces a 15–20% spine shrinkage within a timeframe of 40 min, which is measured as a decrease in spine volume without a concomitant change in either spine diameter or length (Figures 4f and g; Supplementary Figures 6E and F).”

    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 [38]

    The Results section (page unavailable) reports significant spine shrinkage after 20 μM NMDA plus 20 μM glycine, and the Methods describe a 3-minute application followed by 40 minutes before fixation. But the paper measures cross-sectional area, not volume, and does not report unchanged spine diameter or length under this treatment; its live-imaging result of 19% shrinkage is at 52 minutes, not 40. (LLM, conf=0.88)

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Authors
Nakamura, Y., Wood, C. L., Patton, A. P., Jaafari, N., Henley, J. M., Mellor, J. R., & Hanley, J. G.
Affiliations
University of Bristol (GB)
Corresponding author
Hanley, Jonathan G
Venue
The EMBO Journal
Published
2011-01-21
Volume
30
Issue
4
Pages
719-730
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W1930654099
Cited by
97
References
40
Citations by year
2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 8 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 17 · 2013: 16 · 2012: 8
FWCI
6.10
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Bristol Research (University of Bristol) (publishedVersion)
  • Explore Bristol Research (submittedVersion)
Funders
  • Wellcome Trust (083721)
  • Engineering and Physical Sciences Research Council (EP/E500110/1)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
PICK1, Arp2/3 complex, synaptic plasticity, long-term depression, actin polymerization, actin depolymerization, NMDA receptor, AMPA receptor trafficking, hippocampal neurons, spine dynamics, structural plasticity
MeSH terms
Animals, Animals, Newborn, Carrier Proteins, Cells, Cultured, Cytoskeletal Proteins, Embryo, Mammalian, Neuronal Plasticity, Neurons, Nuclear Proteins, Synapses, Receptors, N-Methyl-D-Aspartate, Rats, Wistar, RNA, Small Interfering, Dendritic Spines, Actin-Related Protein 2-3 Complex, Rats, Organelle Size

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