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Cited by 27Protein Kinase Regulation and GTPase SignalingNeuroscience and Neuropharmacology ResearchCellular Mechanics and Interactions

Signaling pathways controlling the phosphorylation state of WAVE1, a regulator of actin polymerization

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Ceglia, Ilaria, Kim, Yong, Nairn, Angus C., Greengard, Paul·2010·Journal of Neurochemistry
DOI 10.1111/j.1471-4159.2010.06743.xPMC PMC2945298
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Abstract

J. Neurochem. (2010) 114, 182–190. The Wiskott‐Aldrich syndrome protein (WASP)‐family verprolin homologous protein 1 (WAVE1) is a key regulator of Arp (actin‐related protein) 2/3 complex‐mediated actin polymerization. We have established previously that the state of phosphorylation of WAVE1 at three distinct residues controls its ability to regulate actin polymerization and spine morphology. Cyclin‐dependent kinase 5 phosphorylates WAVE1 at Ser310, Ser397 and Ser441 to a high basal stoichiometry, resulting in inhibition of WAVE1 activity. Our previous and current studies show that WAVE1 can be dephosphorylated at all three sites and thereby activated upon stimulation of the D1 subclass of dopamine receptors and of the NMDA subclass of glutamate receptors, acting through cAMP and Ca 2+ signaling pathways, respectively. Specifically, we have identified protein phosphatase‐2A and protein phosphatase‐2B as the effectors for these second messengers. These phosphatases act on different sites to mediate receptor‐induced signaling pathways, which would lead to activation of WAVE1.

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  • CK2 phosphorylation of the WCA domain of WAVEs and/or CDK5 phosphorylation of the proline-rich region of WAVE1 may confer an inhibitory state, whereas protein phosphatase-mediated dephosphorylation of these sites may activate the WAVE complex.

    “Thus, CK2 phosphorylation of the WCA domain of WAVEs and/or CDK5 phosphorylation of the proline-rich region of WAVE1 may confer an inhibitory state, whereas protein phosphatase-mediated dephosphorylation of these sites may activate the WAVE complex22,43,44,48,49.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [44]

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  • Upon stimulation of dopamine D1 receptors or NMDA glutamate receptors in brain slices, cAMP and calcium signaling and downstream PP2A and PP2B dephosphorylate WAVE1, indicating the critical involvement of protein phosphatases in neuronal activity-induced WAVE1 activation.

    “Upon stimulation of dopamine D1 receptors (DRD1) or NMDA glutamate receptors in brain slices, cAMP and calcium signaling and downstream protein phosphatase-2A (PP2A) and PP2B dephosphorylate WAVE1, indicating the critical involvement of protein phosphatases in neuronal activity-induced WAVE1 activation44 (Figs. 2 and 3a).”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [44]

  • WAVE1, a downstream effector of NMDA receptor signaling, is a critical mediator of cognitive function.

    “WAVE1, a downstream effector of NMDA receptor signaling44, is a critical mediator of cognitive function.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [44]

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Authors
Ceglia, I., Kim, Y., Nairn, A. C., & Greengard, P.
Affiliations
  • Rockefeller University (US)
  • Yale University (US)
Corresponding author
  • Kim, Yong
  • Greengard, Paul
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2010-06-08
Volume
114
Issue
1
Pages
182-190
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/j.1471-4159.2010.06743.x
PMC
PMC2945298
OpenAlex
W1585638630
Cited by
27
References
3
Citations by year
2026: 1 · 2025: 1 · 2023: 2 · 2021: 1 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 6 · 2014: 1 · 2013: 2 · 2012: 1
FWCI
0.97
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Drug Abuse (DA10044, P01DA010044)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
WAVE1, Arp2/3 complex, actin polymerization, phosphorylation, cyclin-dependent kinase 5, dephosphorylation, protein phosphatase 2A, calcineurin, dopamine D1 receptor, NMDA receptor, cAMP signaling, calcium signaling, dendritic spine morphology
MeSH terms
Actins, Animals, Biopolymers, Corpus Striatum, Colforsin, Male, Mice, Inbred C57BL, Phosphorylation, Signal Transduction, Calcineurin, Wiskott-Aldrich Syndrome Protein Family, Mice, Protein Phosphatase 1, Protein Phosphatase 2, In Vitro Techniques

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