Affinage

CAMK2A

Calcium/calmodulin-dependent protein kinase type II subunit alpha · UniProt Q9UQM7

Length
478 aa
Mass
54.1 kDa
Annotated
2026-06-09
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CaMKIIα is a Ca2+/calmodulin-activated Ser/Thr kinase that functions as a central transducer of synaptic activity, converting Ca2+ signals into persistent changes in synaptic strength and structure (PMID:21059908, PMID:29100089). Its holoenzyme is built from a thermally stable, self-oligomerizing hub domain that assembles the multimeric enzyme and a kinase domain that is autoinhibited by a regulatory segment, with the kinase domain unstable in isolation but markedly stabilized by the regulatory segment within the holoenzyme (PMID:29784083, PMID:32282091); in living neurons the catalytic domains transition from a paired (autoinhibited) to unpaired (active) conformation upon glutamate receptor activation, a flip-flop switch consistent with persistent activity (PMID:19339497). Thr286 autophosphorylation gates this autonomous activity and is bi-directionally tuned by NMDAR-driven Ca2+ and opposing phosphatases (PMID:22582824), and tightly regulated Thr286 phosphorylation is required for neuronal migration and function (PMID:29100089). Activity recruits CaMKIIα into the postsynaptic density through phase separation with Shank3 and Ca2+-dependent, GluN2B-mediated condensate formation with PSD-95, enabling structural LTP (PMID:33235361, PMID:32019829), and stimulus strength together with calcineurin directs CaMKIIα to either excitatory or inhibitory synapses to control receptor surface expression (PMID:21059908). Once positioned, CaMKIIα phosphorylates a broad substrate set to remodel synaptic signaling: GluN2A at Ser1459 to promote SNX27-retromer–dependent NMDAR recycling (PMID:32877683, PMID:34233182), GluN2B (PMID:24032403), long Homer proteins to control mGluR5 scaffolds (PMID:26670047), and RPTPα at Ser180/Ser204 downstream of NCAM to drive neurite outgrowth (PMID:18809727). Its function depends on dendritic localization of its own 3'UTR-bearing mRNA, whose stability and branch-specific translation are governed by mTOR and HuD; disrupting dendritic mRNA targeting depletes synaptic CaMKIIα and impairs late-phase LTP and memory (PMID:12408852, PMID:25944900). De novo CAMK2A mutations that alter catalytic activity, Thr286 autophosphorylation, regulatory-segment autoinhibition, or hub-domain oligomerization cause autism, intellectual disability, and neurodevelopmental disorders (PMID:28130356, PMID:29100089, PMID:29560374, PMID:29784083). Beyond the nervous system, CaMKIIα also acts in non-canonical Wnt signaling by phosphorylating B-raf (PMID:29352270), in lung adenocarcinoma by phosphorylating EZH2 at T487 to de-repress SOX2 (PMID:32483123), and in TNBC metastasis downstream of PDSS1/CoQ10 to drive STAT3 signaling (PMID:34408002). The hub domain is a pharmacologically targetable site bound by GHB analogs that confer neuroprotection under pathological hyperactivation (PMID:34330837, PMID:36346645).

Mechanistic history

Synthesis pass · year-by-year structured walk · 30 steps
  1. 1998 High

    Established how the predominantly cytosolic CaMKIIα is anchored at synaptic actin, showing that subcellular targeting is supplied in trans by the actin-binding CaMKIIβ isoform via hetero-oligomerization.

    Evidence GFP-tagged isoform live imaging and co-expression with F-actin co-localization in neurons

    PMID:9768845

    Open questions at the time
    • Does not address how the holoenzyme is recruited specifically to the PSD
    • Stoichiometry of α/β in native holoenzymes not resolved
  2. 2002 High

    Demonstrated that dendritic mRNA localization, not just protein, is required for synaptic CaMKIIα function, linking a 3'UTR-encoded RNA transport signal to PSD targeting, LTP and memory.

    Evidence Knock-in mouse with mutated endogenous 3'UTR, PSD fractionation, LTP electrophysiology, behavior

    PMID:12408852

    Open questions at the time
    • RNA-binding factors mediating localization not identified here
    • Local versus somatic translation contribution not separated
  3. 2005 High

    Showed CaMKIIα has subunit-selective effects on NMDAR gating, decreasing NR2A but enhancing NR2B desensitization in an autophosphorylation- and Ca2+-dependent manner, distinguishing substrate-specific receptor regulation.

    Evidence Whole-cell patch-clamp in HEK293 with NMDAR subunits and K42R/T286A mutants, BAPTA loading

    PMID:15866054

    Open questions at the time
    • Heterologous system may not reflect native PSD context
    • Phosphorylation sites mediating the effect not mapped
  4. 2008 High

    Identified RPTPα as a CaMKIIα substrate downstream of NCAM, defining a kinase-phosphatase relay in which CaMKIIα phosphorylation increases RPTPα activity to drive neurite outgrowth.

    Evidence Reciprocal co-IP, Ser180/Ser204 phosphorylation assays, S180A/S204A mutants, neurite outgrowth

    PMID:18809727

    Open questions at the time
    • In vivo relevance for axon guidance not tested
    • Single lab
  5. 2009 Medium

    Resolved the conformational basis of persistent activation by directly imaging a paired-to-unpaired catalytic domain transition in neurons upon receptor stimulation.

    Evidence Fluorescence anisotropy and FRET imaging of Venus-tagged CaMKIIα with glutamate stimulation

    PMID:19339497

    Open questions at the time
    • Model relies on structural prediction; atomic confirmation not provided
    • Relationship to Thr286 autophosphorylation not directly linked
  6. 2009 Medium

    Revealed a non-neuronal autoinhibitory role in sperm: CaMKIIα sequestered on MUPP1 PDZ domains suppresses premature acrosomal exocytosis until Ca2+/CaM releases it.

    Evidence Co-localization, PDZ domain binding mapping, CaMKII inhibition, acrosomal exocytosis assays in mouse sperm

    PMID:19934217

    Open questions at the time
    • Direct exocytosis substrate of CaMKIIα not identified
    • Single lab
  7. 2012 Medium

    Established bi-directional control of Thr286 autophosphorylation by NMDAR signal strength, with low Ca2+ promoting and high Ca2+ triggering phosphatase-mediated dephosphorylation.

    Evidence Pharmacological NMDAR subunit manipulation, phosphatase inhibitor profiling, p-Thr286 immunoblotting in cortical neurons

    PMID:22582824

    Open questions at the time
    • Identity of the high-OA-sensitive phosphatase not defined
    • Mechanistic basis for concentration switch unresolved
  8. 2012 Medium

    Identified Abi1 as a resting-state binding partner whose tSNARE domain mimics the CaMKIIα regulatory segment, mutually inhibiting kinase and Rac signaling until Ca2+ dissociates the complex during spine maturation.

    Evidence Co-IP, kinase activity assays, Ser88 phospho-site mutagenesis, Rac assays, spine morphology in hippocampal neurons

    PMID:22993434

    Open questions at the time
    • In vivo role in spine maturation not tested
    • Single lab
  9. 2013 Medium

    Defined an mGluR5→GluN2B switch in which Ca2+ activation releases CaMKIIα from mGluR5 and recruits it to GluN2B for phosphorylation, coupling metabotropic and ionotropic receptor signaling.

    Evidence Pulldown, co-IP in striatal neurons, Ca2+ manipulation, GluN2B phosphorylation assay

    PMID:24032403

    Open questions at the time
    • GluN2B phospho-site not mapped here
    • Functional plasticity consequence not measured
  10. 2013 Medium

    Characterized rapid, actin-dependent somatic clustering of endogenous CaMKIIα that disperses with Ca2+, distinguishing somatic dynamics from dendritic trafficking.

    Evidence mRNA-display-selected recombinant probe imaging in living cortical neurons, cytochalasin D, Ca2+ imaging

    PMID:24005308

    Open questions at the time
    • Functional purpose of somatic clusters unknown
    • Single lab
  11. 2013 Medium

    Linked CaMKIIα expression to mood-related circuitry, showing ΔFosB epigenetic control of the CaMKIIα promoter in NAc determines antidepressant responses.

    Evidence ChIP, viral overexpression/inhibition in NAc, chronic social defeat stress

    PMID:24240473

    Open questions at the time
    • Downstream NAc substrates of CaMKII not defined
    • Causal histone marks not separated from ΔFosB binding
  12. 2014 High

    Extended CaMKIIα substrate range to the pain receptor P2X3, identifying Thr388 phosphorylation that promotes caveolin-1–dependent membrane insertion.

    Evidence Thr388 mutagenesis, in vitro kinase assay, co-IP, caveolin-1 knockdown, surface trafficking in HEK293T and sensory neurons

    PMID:24755854

    Open questions at the time
    • In vivo nociceptive role not established here
    • Single lab
  13. 2015 High

    Identified IRBIT as a calmodulin-competitive inhibitor of CaMKIIα, with loss causing excess TH phosphorylation and dopaminergic behavioral abnormalities, defining an endogenous brake on kinase activity.

    Evidence Co-IP, in vitro kinase and CaM-competition assays, IRBIT KO mice, TH phosphorylation in VTA

    PMID:25922519

    Open questions at the time
    • Direct TH phospho-site by CaMKIIα not mapped
    • Single lab
  14. 2015 Medium

    Defined the mTOR/HuD axis that stabilizes CaMKIIα mRNA poly(A) tails and drives branch-specific dendritic expression, providing a molecular basis for synaptic tagging and capture.

    Evidence Rapamycin treatment, poly(A) tail assays, HuD domain-deletion mutants, dendritic mRNA/protein quantification

    PMID:25944900

    Open questions at the time
    • Link to in vivo plasticity not tested here
    • Single lab
  15. 2015 High

    Showed that pathological elevation of CaMKIIα hyperphosphorylates Homer to disrupt mGluR5 scaffolds, and that CaMKIIα inhibition rescues Fragile X circuit hyperexcitability.

    Evidence Protein quantification, Homer phosphorylation, KN-93 and genetic inhibition, EEG in Fmr1 KO mice

    PMID:26670047

    Open questions at the time
    • Homer phospho-sites not mapped
    • Whether elevated CaMKIIα is cause or consequence in other disease contexts unclear
  16. 2017 High

    Connected CaMKIIα to disease by showing the ASD-linked E183V catalytic mutation acts dominant-negatively, reduces partner binding, and produces synaptic and behavioral deficits in knock-in mice.

    Evidence In vitro kinase assays, co-IP, knock-in mouse, fractionation, morphology, electrophysiology, behavior

    PMID:28130356

    Open questions at the time
    • Mechanism of accelerated turnover not defined
    • Generalizability to other catalytic variants untested
  17. 2017 High

    Established CAMK2A as a neurodevelopmental disorder gene, showing that bidirectional dysregulation of Thr286 autophosphorylation impairs neuronal migration.

    Evidence Whole-exome sequencing, biochemical autophosphorylation assays of variants, neuronal migration assays

    PMID:29100089

    Open questions at the time
    • Substrate(s) controlling migration not identified
    • Why both gain and loss of Thr286 phosphorylation are pathogenic not mechanistically resolved
  18. 2017 Medium

    Defined a synaptic targeting function for CaMKIIα Cys280/Cys289 S-nitrosation, which promotes synaptosomal accumulation and downstream GluR1 phosphorylation needed for LTP.

    Evidence S-nitrosation site mutagenesis, synaptosomal fractionation, GSNOR transgenic/KO mice, LTP, behavior

    PMID:28883020

    Open questions at the time
    • Structural effect of nitrosation on holoenzyme not resolved
    • Single lab
  19. 2017 Medium

    Linked regulatory-segment integrity to disease, showing exon 11 skipping deletes the autoinhibitory segment and missense variants increase Thr286 phosphorylation and alter A-type K+ currents.

    Evidence Minigene splicing assay, structural modeling, Neuro-2a immunoblotting, hippocampal neuron electrophysiology

    PMID:29560374

    Open questions at the time
    • Mechanism linking hyperactive CaMKIIα to K+ current change not defined
    • Single lab
  20. 2018 High

    Established the hub domain's essential oligomerization role by showing the His477Tyr variant cannot assemble the holoenzyme and fails to support neuronal function across worm and human iPSC models.

    Evidence Self-oligomerization assay, C. elegans unc-43 complementation, patient iPSC-derived neurons

    PMID:29784083

    Open questions at the time
    • Quantitative relationship between assembly defect and synaptic deficit not resolved
    • Single variant
  21. 2018 High

    Mapped the structural basis of CaMKIIα–mGlu5 coupling, showing activated CaMKIIα binds a tribasic KRR motif and increases mGlu5 surface expression and Ca2+ signaling kinetics.

    Evidence Pulldown with purified proteins, co-IP, KRR→AAA mutagenesis, surface biotinylation, Ca2+ imaging

    PMID:30282777

    Open questions at the time
    • In vivo synaptic consequence not tested
    • Single lab
  22. 2018 Medium

    Extended CaMKIIα to non-canonical Wnt signaling, identifying B-raf as a substrate that activates ERK1/2 to drive chondrocyte de-differentiation.

    Evidence Co-IP, in vitro B-raf phosphorylation, siRNA, ERK1/2 activation assays

    PMID:29352270

    Open questions at the time
    • B-raf phospho-site not mapped
    • Single lab
  23. 2020 High

    Provided biophysical architecture of the holoenzyme, quantifying domain-specific thermal stability and how the regulatory segment stabilizes the kinase while the hub is destabilized in context.

    Evidence Differential scanning calorimetry, X-ray crystallography, mass photometry

    PMID:32282091

    Open questions at the time
    • Functional consequence of reciprocal stabilization not tested in cells
    • Single lab
  24. 2020 Medium

    Demonstrated that CaMKIIα is recruited to the PSD by phase separation with Shank3 and forms Ca2+-dependent GluN2B/PSD-95 condensates that drive structural LTP, with phosphatases controlling nano-domain shuttling.

    Evidence Phase separation assays, live imaging, FRAP, co-IP, phosphatase inhibitors, structural LTP

    PMID:33235361

    Open questions at the time
    • In vivo verification of condensates lacking
    • Single lab
  25. 2020 High

    Mapped direct Shank3–CaMKIIα binding (Shank3 949RRK951) and showed it enables depolarization-induced membrane-to-nucleus CREB/c-Fos signaling.

    Evidence Co-IP from forebrain, in vitro binding, alanine mutagenesis, shRNA/rescue, CREB phosphorylation and c-Fos assays

    PMID:32019829

    Open questions at the time
    • Mechanism transmitting signal to nucleus not fully defined
    • Single lab
  26. 2020 High

    Identified GluN2A Ser1459 as a CaMKIIα substrate that recruits the SNX27-retromer to recycle GluN2A-NMDARs to the surface during LTP, replicated and extended in a companion study including an epilepsy variant.

    Evidence In vitro kinase assay, phospho-site mutagenesis, co-IP, SNX27 knockdown, surface NMDAR quantification, electrophysiology

    PMID:32877683 PMID:34233182

    Open questions at the time
    • Other retromer cargoes regulated by CaMKIIα unknown
    • In vivo memory consequence of S1459 phosphorylation not tested
  27. 2020 Medium

    Revealed a cancer kinase function: CaMKIIα phosphorylates EZH2 at T487 to suppress its methyltransferase activity, de-repressing SOX2 and supporting tumor-initiating cells in lung adenocarcinoma.

    Evidence Phosphorylation assay, ChIP for H3K27me3/EZH2, tumor-initiating cell assays in vitro and in vivo

    PMID:32483123

    Open questions at the time
    • Upstream activator of CaMKIIα in tumors not defined here
    • Single lab
  28. 2021 Medium

    Placed CaMKIIα in a metabolic-oncogenic cascade, showing PDSS1/CoQ10-driven Ca2+ activates CaMKIIα to phosphorylate STAT3 and promote TNBC metastasis.

    Evidence PDSS1 knockdown, catalytic mutant, CaMKIIα and STAT3 phosphorylation assays, metastasis model

    PMID:34408002

    Open questions at the time
    • Direct STAT3 phospho-site by CaMKIIα not mapped
    • Single lab
  29. 2021 High

    Established the hub domain as a druggable allosteric site, solving a crystal structure of GHB-analog binding that thermally stabilizes the hub and confers neuroprotection selectively under hyperactivation.

    Evidence Photoaffinity labeling, chemical proteomics, 2.2-Å X-ray structure, DSF, excitotoxicity and MCAO models

    PMID:34330837

    Open questions at the time
    • Mechanism linking hub stabilization to reduced pathological activity not fully defined
    • Selectivity over other CaMKII isoforms not detailed
  30. 2024 Medium

    Advanced hub-domain pharmacology with a brain-penetrant ligand (Ph-HTBA) that binds at mid-nanomolar affinity and induces a Trp403 conformational flip, validating the hub as a tractable CNS target.

    Evidence Binding affinity, thermal shift, SAR informed by crystallography, in vivo brain penetration (Kp,uu)

    PMID:36346645

    Open questions at the time
    • Therapeutic efficacy in disease models not shown here
    • Functional kinase consequence of Trp403 flip not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse substrate phosphorylation events, condensate dynamics, and bidirectional Thr286 regulation are integrated to encode specific synaptic and behavioral plasticity outcomes in vivo remains unresolved.
  • No unified in vivo map linking individual substrate phosphorylations to plasticity readouts
  • Mechanism distinguishing physiological vs pathological hyperactivation incompletely defined
  • Substrate selectivity rules for the activated holoenzyme not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016740 transferase activity 5 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-1643685 Disease 6 R-HSA-112316 Neuronal System 5 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-4839726 Chromatin organization 1
Partners
ABI1DLG4EZH2GRIN2BGRM5MPDZPTPRASHANK3
Complex memberships
CaMKII holoenzyme (dodecameric hub-assembled)CaMKIIα/GluN2B/PSD-95 condensateNCAM/RPTPα/CaMKIIα complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 CaMKIIβ binds F-actin in dendritic spines and cell cortex while CaMKIIα is largely cytosolic; when co-expressed, the two isoforms form large heterooligomers, and a small fraction of CaMKIIβ is sufficient to dock the predominant CaMKIIα to the actin cytoskeleton, establishing CaMKIIβ as a targeting module for CaMKIIα localization. GFP-tagged CaMKII isoform live imaging, co-expression in neurons, F-actin co-localization assays Neuron High 9768845
2002 Dendritic localization of CaMKIIα mRNA (via its 3'UTR signal) is required for normal postsynaptic density targeting of the protein; disrupting dendritic mRNA localization dramatically reduces CaMKIIα in PSDs and impairs late-phase LTP, spatial memory, fear conditioning, and object recognition memory. Knock-in mouse with mutated endogenous CaMKIIα 3'UTR, PSD fractionation, LTP electrophysiology, behavioral testing Neuron High 12408852
2005 CaMKIIα enhances the desensitization of NR2B-containing NMDA receptors in an autophosphorylation-dependent manner; kinase-dead (K42R) and autophosphorylation-deficient (T286A) mutants fail to enhance desensitization, and Ca2+ chelation with BAPTA abrogates the effect. CaMKIIα decreases (rather than increases) desensitization of NR2A-containing receptors. Whole-cell patch-clamp electrophysiology in HEK293 cells co-expressing NMDA receptor subunits and CaMKIIα mutants, BAPTA loading Molecular and cellular neurosciences High 15866054
2008 NCAM clustering activates CaMKIIα via Ca2+ influx through associated voltage-dependent Ca2+ channels; activated CaMKIIα forms a complex with NCAM and RPTPα and phosphorylates RPTPα at Ser180/Ser204, increasing RPTPα phosphatase activity, which is required for NCAM-induced neurite outgrowth. Co-immunoprecipitation, serine phosphorylation assays, dominant-negative RPTPα mutants (S180A/S204A), neurite outgrowth assays The Journal of cell biology High 18809727
2009 CaMKIIα colocalizes with MUPP1 in the acrosomal region of spermatozoa and selectively binds PDZ domains 10–11 of MUPP1; Ca2+/calmodulin releases CaMKIIα from MUPP1, and competitive displacement of CaMKIIα from these PDZ domains (or CaMKII catalytic inhibition) triggers spontaneous acrosomal exocytosis, indicating CaMKIIα normally suppresses premature acrosomal secretion. Co-localization, in vitro binding assays mapping PDZ domain specificity, CaMKII inhibitor experiments, acrosomal exocytosis assays in mouse spermatozoa Journal of cell science Medium 19934217
2009 CaMKIIα catalytic domains form paired (autoinhibited) and unpaired (active) conformations in living neurons; glutamate receptor activation triggers a structural transition from paired to unpaired conformation, consistent with a flip-flop switch model of persistent kinase activation. Fluorescence anisotropy and FRET imaging of Venus-tagged CaMKIIα in neurons, glutamate receptor stimulation Proceedings of the National Academy of Sciences of the United States of America Medium 19339497
2010 CaMKIIα selectively translocates to inhibitory (GABAergic) synapses in response to moderate NMDAR activation that triggers GABAAR insertion; Thr286 autophosphorylation is necessary and sufficient to localize CaMKIIα at inhibitory synapses and enhance surface GABAAR expression. Stronger glutamatergic stimulation (coupled to AMPAR insertion) also causes Thr286 autophosphorylation but prevents accumulation at inhibitory synapses via calcineurin. Fluorescence imaging of CaMKIIα translocation in CA1 neurons, pharmacological NMDAR stimulation paradigms, phosphomimetic/phosphodeficient mutants, calcineurin inhibitor experiments, surface GABAAR quantification Proceedings of the National Academy of Sciences of the United States of America High 21059908
2012 CaMKIIα interacts with Abi1 under resting conditions through the Abi1 tSNARE domain, which shares homology with the CaMKIIα regulatory domain; this interaction simultaneously inhibits CaMKIIα activity and Abi1-dependent Rac activation. Glutamate receptor activation dissociates the complex via calmodulin binding, and CaMKIIα phosphorylates Abi1 at Ser88 prior to dissociation, contributing to spine maturation. Co-immunoprecipitation, kinase activity assays, phosphorylation site mutagenesis, Rac activation assays, spine morphology analysis in rat hippocampal neurons The Journal of neuroscience Medium 22993434
2013 ΔFosB binds the CaMKIIα gene promoter in nucleus accumbens (NAc); chronic fluoxetine reduces ΔFosB binding at the CaMKIIα promoter by inducing histone H3 acetylation decreases and H3K9 dimethylation increases at that locus, suppressing CaMKIIα expression. CaMKII overexpression in NAc blocks fluoxetine's antidepressant effects, while CaMKII inhibition in NAc mimics fluoxetine. Chromatin immunoprecipitation (ChIP), viral overexpression/inhibition in NAc, chronic social defeat stress paradigm Neuropsychopharmacology Medium 24240473
2013 Inactive CaMKIIα constitutively binds the proximal intracellular C-terminal tail of mGluR5 in striatal neurons; Ca2+ activation of CaMKIIα causes its dissociation from mGluR5 and simultaneous recruitment to the adjacent GluN2B subunit of NMDARs, enabling CaMKIIα to phosphorylate GluN2B at a CaMKII-sensitive site. In vitro pulldown, co-immunoprecipitation in striatal neurons, Ca2+ manipulation, GluN2B phosphorylation assay Journal of neurochemistry Medium 24032403
2013 In neuronal somata, CaMKIIα forms actin-dependent clusters (~1–4 µm) under basal conditions that disperse in a Ca2+-dependent manner within seconds of glutamate/glycine exposure and reform after washout; these clusters are distinct from the dendritic trafficking behavior of CaMKIIα. Novel recombinant probe (mRNA-display selected) labeling endogenous CaMKIIα in living rat cortical neurons, cytochalasin D actin disruption, Ca2+ imaging The Journal of neuroscience Medium 24005308
2015 IRBIT binds to CaMKIIα and suppresses its kinase activity by inhibiting calmodulin binding; IRBIT-deficient mice show elevated CaMKIIα-mediated phosphorylation of tyrosine hydroxylase (TH) in the ventral tegmental area, leading to increased catecholamine levels, hyperlocomotion, and social abnormalities. Co-immunoprecipitation, in vitro kinase activity assays, calmodulin binding competition assays, IRBIT knockout mice, TH phosphorylation analysis in VTA Proceedings of the National Academy of Sciences of the United States of America High 25922519
2015 mTOR activity preserves the poly(A) tail length of CaMKIIα mRNA, preventing its deadenylation; the RNA-stabilizing protein HuD (via its poly(A)-binding third RRM domain) captures CaMKIIα mRNA and promotes its branch-specific dendritic expression, providing a molecular mechanism for synaptic tagging and capture. mTOR inhibition (rapamycin) in neurons, poly(A) tail assays, HuD overexpression/deletion mutants, dendritic CaMKIIα protein/mRNA quantification The Journal of biological chemistry Medium 25944900
2015 Elevated CaMKIIα protein in Fmr1 KO cortex causes hyperphosphorylation of long Homer proteins, disrupting mGluR5–Homer scaffolds at synapses; genetic or pharmacological inhibition of CaMKIIα restores mGluR5–Homer scaffolds and rescues circuit hyperexcitability/seizures in Fmr1 KO mice. CaMKIIα protein level quantification, Homer phosphorylation assays, CaMKIIα inhibitor (KN-93) and genetic inhibition, EEG/circuit excitability recordings in Fmr1 KO mice Cell reports High 26670047
2017 A de novo ASD-linked CaMKIIα E183V mutation in the catalytic domain reduces substrate phosphorylation and autophosphorylation, acts as a dominant-negative suppressor of wild-type CaMKIIα autophosphorylation, reduces binding to Shank3, L-type calcium channel subunits, and NMDAR subunits, and increases CaMKIIα turnover. Knock-in mice show reduced synaptic CaMKIIα, lower spine density, decreased excitatory synaptic transmission, hyperactivity, social deficits, and repetitive behaviors. In vitro kinase assays, co-immunoprecipitation, knock-in mouse model, subcellular fractionation, neuronal morphology analysis, electrophysiology, behavioral testing The Journal of neuroscience High 28130356
2017 De novo CAMK2A mutations identified in intellectual disability patients alter CaMKIIα auto-phosphorylation at Thr286 (either increasing or decreasing it), and all mutations affecting auto-phosphorylation also impair neuronal migration, establishing that tightly regulated Thr286 auto-phosphorylation is required for neuronal function and neurodevelopment. Whole-exome sequencing, biochemical autophosphorylation assays in patient-derived variants, neuronal migration assays American journal of human genetics High 29100089
2017 A splice-site CAMK2A variant in a neurodevelopmental disorder patient causes exon 11 skipping, deleting the regulatory segment responsible for CaMKII autoinhibition; missense variants predicted to disrupt kinase domain–regulatory segment interactions increase Thr286 phosphorylation in Neuro-2a cells, and a CaMKIIα mutant expressed in hippocampal neurons significantly increases A-type K+ currents, facilitating spike repolarization. Minigene splicing assay, structural modeling, immunoblotting in Neuro-2a cells, electrophysiology in primary hippocampal neurons Annals of clinical and translational neurology Medium 29560374
2018 The CAMK2A missense mutation p.His477Tyr (in the association/hub domain) is defective in self-oligomerization and unable to assemble into the multimeric holoenzyme; in vivo, it fails to rescue neuronal defects in C. elegans unc-43 mutants, and iPSC-derived neurons from the patient display profound synaptic defects. Biochemical self-oligomerization assay, C. elegans complementation (unc-43 ortholog), patient iPSC-derived neuron synaptic analysis eLife High 29784083
2018 Activated (Thr286-autophosphorylated) CaMKIIα directly binds the membrane-proximal C-terminal domain of mGlu5a via a tribasic KRR motif (K866-R-R868); mutation of this motif reduces co-immunoprecipitation of CaMKIIα with full-length mGlu5a, and CaMKIIα increases mGlu5a surface expression and modulates the kinetics of mGlu5a-mediated Ca2+ mobilization. In vitro pulldown with purified proteins, co-immunoprecipitation in heterologous cells, site-directed mutagenesis (KRR→AAA), cell-surface biotinylation, Ca2+ fluorimetry and single-cell Ca2+ imaging Molecular pharmacology High 30282777
2020 GHB analogs bind selectively to the CaMKIIα hub domain at a site revealed by a 2.2-Å X-ray crystal structure; binding promotes concentration-dependent increases in hub thermal stability and provides significant neuroprotection selectively under pathological CaMKIIα hyperactivation (excitotoxicity and cerebral ischemia), establishing the hub domain as a pharmacologically targetable site. Photoaffinity labeling, chemical proteomics, X-ray crystallography (2.2 Å), differential scanning fluorimetry (thermal stability), in vitro excitotoxicity assays, MCAO mouse model Proceedings of the National Academy of Sciences of the United States of America High 34330837
2020 Under basal conditions CaMKIIα is recruited to the Shank3 subcompartment of the PSD via phase separation; Ca2+ rise induces GluN2B-mediated recruitment of active CaMKIIα forming CaMKIIα/GluN2B/PSD-95 condensates that autonomously disperse upon Ca2+ removal. Protein phosphatases control Ca2+-dependent shuttling of CaMKIIα between PSD nano-domains, and CaMKIIα activation further enlarges PSD assembly and induces structural LTP. Phase separation assays, live-cell imaging, FRAP, co-immunoprecipitation, phosphatase inhibitor experiments, structural LTP induction Cell research Medium 33235361
2020 Shank3 directly binds activated CaMKIIα between residues 829–1130 of Shank3; mutation of Shank3 residues 949RRK951 to alanines abolishes CaMKII binding in vitro and in cells. This CaMKII–Shank3 interaction, together with Shank3–LTCC interaction, is required for depolarization-induced CREB phosphorylation and c-Fos expression in hippocampal neurons (long-range plasma membrane–to–nucleus signaling). Co-immunoprecipitation from mouse forebrain, in vitro direct binding with purified proteins, alanine substitution mutagenesis, shRNA/rescue in hippocampal neurons, nuclear CREB phosphorylation and c-Fos assays The Journal of neuroscience High 32019829
2020 CaMKIIα phosphorylates GluN2A at Ser1459 in response to synaptic activity mimicking LTP; Ser1459 phosphorylation promotes GluN2A interaction with the SNX27-retromer complex, enhancing endosomal recycling of GluN2A-NMDARs to the neuronal surface. Loss of CaMKIIα function blocks the glycine-induced increase in surface GluN2A-NMDARs. In vitro kinase assay, phosphorylation site mutagenesis, co-immunoprecipitation, SNX27 knockdown, surface NMDAR quantification, synaptic current recordings Cell reports High 32877683 34233182
2020 CaMKIIα holoenzyme stability is characterized by differential domain stability: the kinase domain alone is thermally unstable (Tm ~36°C), stabilized moderately by ATP/MgCl2 (Tm ~40°C) and markedly by the regulatory segment (Tm ~60°C); the hub domain alone is highly stable (Tm ~90°C); within the holoenzyme the kinase domain is stabilized and the hub domain is destabilized. A crystal structure of the kinase domain bound to p-coumaric acid reveals solvent-exposed hydrophobic residues in the substrate-binding pocket in the absence of regulatory segment. Differential scanning calorimetry (DSC), X-ray crystallography, mass photometry Protein science High 32282091
2014 CaMKIIα phosphorylates the P2X3 receptor at Thr388 in the C-terminus; this phosphorylation increases P2X3 receptor binding to caveolin-1, and CaMKIIα cooperates with caveolin-1 to drive ATP-induced membrane insertion of P2X3 (and co-insertion of P2X2/P2X3) receptors, increasing surface P2X3 signaling. Mutagenesis of Thr388, in vitro kinase assay, co-immunoprecipitation, caveolin-1 knockdown, surface receptor trafficking assay in HEK293T cells and primary sensory neurons Journal of molecular cell biology High 24755854
2017 S-nitrosation of CaMKIIα (at Cys280/Cys289) promotes its synaptosomal accumulation; GSNOR (S-nitrosoglutathione reductase) overexpression in neurons decreases CaMKIIα S-nitrosation and reduces CaMKIIα in synaptosomal fractions along with downstream p(S831)-GluR1, impairing LTP and cognition. Mutation of the S-nitrosation sites (C280/C289) recapitulates reduced synaptosomal accumulation. S-nitrosation site mutagenesis, synaptosomal fractionation, GSNOR transgenic/KO mice, LTP electrophysiology, behavioral testing The Journal of neuroscience Medium 28883020
2018 Non-canonical Wnt-3a signals through Frizzled-6/DVL-2/syndecan-4 to recruit CaMKIIα to syndecan-4; CaMKIIα phosphorylates B-raf in vitro and in vivo, activating ERK1/2 signaling and driving chondrocyte de-differentiation. Co-immunoprecipitation, in vitro kinase assay demonstrating CaMKIIα phosphorylation of B-raf, siRNA knockdown, ERK1/2 activation assays Cell death and differentiation Medium 29352270
2020 CAMK2A phosphorylates EZH2 at T487 in a kinase-dependent manner, suppressing EZH2 methyltransferase activity and reducing H3K27me3 and EZH2 occupancy at the SOX2 locus, leading to epigenetic de-repression of SOX2 and support of tumor-initiating cell phenotypes in lung adenocarcinoma. Kinase-dependent phosphorylation assay, ChIP for H3K27me3 and EZH2, in vitro and in vivo tumor-initiating cell assays Cell death & disease Medium 32483123
2021 PDSS1, via its catalytic product CoQ10 and elevation of intracellular calcium, induces CAMK2A phosphorylation (activation), which is required for STAT3 phosphorylation in the cytoplasm; phosphorylated STAT3 then translocates to the nucleus to promote oncogenic signaling and TNBC metastasis. A catalytically inactive PDSS1 mutant fails to activate CAMK2A. PDSS1 knockdown, catalytic mutant expression, CAMK2A phosphorylation assays, STAT3 phosphorylation/nuclear translocation assays, in vitro migration/invasion, in vivo metastasis model Cancer research Medium 34408002
2021 GluN2A Ser1459 phosphorylation by CaMKIIα (in response to glycine/LTP stimulation) promotes GluN2A-NMDAR interaction with the SNX27-retromer complex for endosomal recycling; the epilepsy-associated S1459G variant abolishes this interaction, reduces spine density, decreases excitatory transmission, and prolongs NMDAR-mediated synaptic current decay by increasing channel open duration. In vitro kinase assay, co-immunoprecipitation, SNX27/CaMKIIα knockdown, surface NMDAR quantification, NMDAR single-channel and synaptic current recordings, spine density analysis Cell reports High 34233182
2012 Bi-directional regulation of CaMKIIα Thr286 autophosphorylation by NMDAR activation: low NMDA concentration (20 µM) up-regulates Thr286 phosphorylation via both NR2A and NR2B, while high concentration (100 µM) causes dephosphorylation via a phosphatase sensitive to high-concentration okadaic acid but not to PP2A or PP2B inhibitors specifically. Pharmacological NMDAR subunit inhibition and knockdown, NR2A/NR2B overexpression, phosphatase inhibitor profiling, immunoblotting of p-Thr286 in cortical neurons Journal of neurochemistry Medium 22582824
2008 CaMKIIα and CaMKIIβ co-expressed with NR1/NR2A or NR1/NR2B receptors do not alter the ethanol inhibition of NMDA receptor currents, and deletion of CaMKII binding domains in NR1 or NR2 or phospho-site mutations does not change ethanol sensitivity (negative result). Whole-cell patch-clamp in HEK293 cells co-expressing CaMKII isoforms and NMDAR subunits, GFP-tagged CaMKII, ethanol concentration-response Alcohol Medium 18562151
2024 The CaMKIIα hub domain contains a discrete small-molecule binding site; the novel ligand Ph-HTBA binds with mid-nanomolar affinity, induces a CaMKIIα Trp403 flip in the hub, markedly stabilizes the hub thermally, is brain-penetrant in mice (Kp,uu = 0.85), and selectively modulates the hub domain. Binding affinity assays, thermal shift assay, X-ray crystallography-informed structure-activity relationship, in vivo brain penetration (Kp,uu measurement) Journal of medicinal chemistry Medium 36346645

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Disruption of dendritic translation of CaMKIIalpha impairs stabilization of synaptic plasticity and memory consolidation. Neuron 418 12408852
1998 CaMKIIbeta functions as an F-actin targeting module that localizes CaMKIIalpha/beta heterooligomers to dendritic spines. Neuron 283 9768845
2001 A CamKIIalpha iCre BAC allows brain-specific gene inactivation. Genesis (New York, N.Y. : 2000) 255 11668676
2010 MicroRNA-148/152 impair innate response and antigen presentation of TLR-triggered dendritic cells by targeting CaMKIIα. Journal of immunology (Baltimore, Md. : 1950) 233 21068402
2013 Distribution of CaMKIIα expression in the brain in vivo, studied by CaMKIIα-GFP mice. Brain research 179 23632380
2017 De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability. American journal of human genetics 153 29100089
2018 LncRNA CamK-A Regulates Ca2+-Signaling-Mediated Tumor Microenvironment Remodeling. Molecular cell 136 30220561
2010 Selective translocation of Ca2+/calmodulin protein kinase IIalpha (CaMKIIalpha) to inhibitory synapses. Proceedings of the National Academy of Sciences of the United States of America 118 21059908
2017 A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors. The Journal of neuroscience : the official journal of the Society for Neuroscience 90 28130356
2011 Independent localization of MAP2, CaMKIIα and β-actin RNAs in low copy numbers. EMBO reports 87 21869818
2013 Fluoxetine epigenetically alters the CaMKIIα promoter in nucleus accumbens to regulate ΔFosB binding and antidepressant effects. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 85 24240473
2018 De novo variants in CAMK2A and CAMK2B cause neurodevelopmental disorders. Annals of clinical and translational neurology 70 29560374
2020 CaMKIIα-driven, phosphatase-checked postsynaptic plasticity via phase separation. Cell research 69 33235361
2009 Structural rearrangement of CaMKIIalpha catalytic domains encodes activation. Proceedings of the National Academy of Sciences of the United States of America 69 19339497
2020 Extrasynaptic CaMKIIα is involved in the antidepressant effects of ketamine by downregulating GluN2B receptors in an LPS-induced depression model. Journal of neuroinflammation 68 32522211
2018 A homozygous loss-of-function CAMK2A mutation causes growth delay, frequent seizures and severe intellectual disability. eLife 61 29784083
2005 CaMKIIalpha enhances the desensitization of NR2B-containing NMDA receptors by an autophosphorylation-dependent mechanism. Molecular and cellular neurosciences 59 15866054
2023 CaMKIIα Promoter-Controlled Circuit Manipulations Target Both Pyramidal Cells and Inhibitory Interneurons in Cortical Networks. eNeuro 55 36963833
2017 Abnormal Microglia and Enhanced Inflammation-Related Gene Transcription in Mice with Conditional Deletion of Ctcf in Camk2a-Cre-Expressing Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 29133437
2004 One-trial aversive learning induces late changes in hippocampal CaMKIIalpha, Homer 1a, Syntaxin 1a and ERK2 protein levels. Brain research. Molecular brain research 51 15548423
2019 Inhibition of CaMKIIα Activity Enhances Antitumor Effect of Fullerene C60 Nanocrystals by Suppression of Autophagic Degradation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 47 31016106
2020 An Epilepsy-Associated GRIN2A Rare Variant Disrupts CaMKIIα Phosphorylation of GluN2A and NMDA Receptor Trafficking. Cell reports 46 32877683
2018 Analysis of the CaMKIIα and β splice-variant distribution among brain regions reveals isoform-specific differences in holoenzyme formation. Scientific reports 46 29615706
2018 Hypoxic preconditioning attenuates necroptotic neuronal death induced by global cerebral ischemia via Drp1-dependent signaling pathway mediated by CaMKIIα inactivation in adult rats. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 46 30148677
2020 Nrf2 promotes esophageal squamous cell carcinoma (ESCC) resistance to radiotherapy through the CaMKIIα-associated activation of autophagy. Cell & bioscience 45 32760495
2015 Elevated CaMKIIα and Hyperphosphorylation of Homer Mediate Circuit Dysfunction in a Fragile X Syndrome Mouse Model. Cell reports 45 26670047
2009 Kynurenate derivative attenuates the nitroglycerin-induced CamKIIα and CGRP expression changes. Headache 45 19925620
2021 GHB analogs confer neuroprotection through specific interaction with the CaMKIIα hub domain. Proceedings of the National Academy of Sciences of the United States of America 42 34330837
2019 The novel circular RNA circ-CAMK2A enhances lung adenocarcinoma metastasis by regulating the miR-615-5p/fibronectin 1 pathway. Cellular & molecular biology letters 40 31889960
2013 Differential regulation of CaMKIIα interactions with mGluR5 and NMDA receptors by Ca(2+) in neurons. Journal of neurochemistry 40 24032403
2015 Mammalian Target of Rapamycin (mTOR) Tagging Promotes Dendritic Branch Variability through the Capture of Ca2+/Calmodulin-dependent Protein Kinase II α (CaMKIIα) mRNAs by the RNA-binding Protein HuD. The Journal of biological chemistry 39 25944900
2015 IRBIT regulates CaMKIIα activity and contributes to catecholamine homeostasis through tyrosine hydroxylase phosphorylation. Proceedings of the National Academy of Sciences of the United States of America 38 25922519
2008 NCAM induces CaMKIIalpha-mediated RPTPalpha phosphorylation to enhance its catalytic activity and neurite outgrowth. The Journal of cell biology 38 18809727
2017 Increased GSNOR Expression during Aging Impairs Cognitive Function and Decreases S-Nitrosation of CaMKIIα. The Journal of neuroscience : the official journal of the Society for Neuroscience 37 28883020
2020 Neuronal L-Type Calcium Channel Signaling to the Nucleus Requires a Novel CaMKIIα-Shank3 Interaction. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 32019829
2020 CaMKIIα-Positive Interneurons Identified via a microRNA-Based Viral Gene Targeting Strategy. The Journal of neuroscience : the official journal of the Society for Neuroscience 36 33158963
2021 PDSS1-Mediated Activation of CAMK2A-STAT3 Signaling Promotes Metastasis in Triple-Negative Breast Cancer. Cancer research 35 34408002
2009 CaMKIIalpha interacts with multi-PDZ domain protein MUPP1 in spermatozoa and prevents spontaneous acrosomal exocytosis. Journal of cell science 35 19934217
2020 miR-142-3p Regulates BDNF Expression in Activated Rodent Microglia Through Its Target CAMK2A. Frontiers in cellular neuroscience 33 32508597
2020 SIRT1 Decreases Emotional Pain Vulnerability with Associated CaMKIIα Deacetylation in Central Amygdala. The Journal of neuroscience : the official journal of the Society for Neuroscience 32 32005763
2016 CaMKIIα underlies spontaneous and evoked pain behaviors in Berkeley sickle cell transgenic mice. Pain 32 27842048
2022 GABAergic CaMKIIα+ Amygdala Output Attenuates Pain and Modulates Emotional-Motivational Behavior via Parabrachial Inhibition. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 35667849
2023 LHPP in Glutamatergic Neurons of the Ventral Hippocampus Mediates Depression-like Behavior by Dephosphorylating CaMKIIα and ERK. Biological psychiatry 30 37678540
2016 Beneficial Effects of a CaMKIIα Inhibitor TatCN21 Peptide in Global Cerebral Ischemia. Journal of molecular neuroscience : MN 30 27604243
2014 Elevated activation of CaMKIIα in the CPEB3-knockout hippocampus impairs a specific form of NMDAR-dependent synaptic depotentiation. Frontiers in cellular neuroscience 29 25404896
2021 Regulation of NMDA receptor trafficking and gating by activity-dependent CaMKIIα phosphorylation of the GluN2A subunit. Cell reports 27 34233182
2020 Rbfox-1 contributes to CaMKIIα expression and intracerebral hemorrhage-induced secondary brain injury via blocking micro-RNA-124. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 27 32248729
2020 CAMK2A supported tumor initiating cells of lung adenocarcinoma by upregulating SOX2 through EZH2 phosphorylation. Cell death & disease 27 32483123
2020 Characterization of CaMKIIα holoenzyme stability. Protein science : a publication of the Protein Society 26 32282091
2018 Role of miR-148a in Mitigating Hepatic Ischemia-Reperfusion Injury by Repressing the TLR4 Signaling Pathway via Targeting CaMKIIα in Vivo and in Vitro. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 26 30244246
2017 Recruitment of Staufen2 Enhances Dendritic Localization of an Intron-Containing CaMKIIα mRNA. Cell reports 26 28683307
2017 CaMKIIα expression in a mouse model of NMDAR hypofunction schizophrenia: Putative roles for IGF-1R and TLR4. Brain research bulletin 26 29137928
2014 mTORC1 inhibition in the nucleus accumbens 'protects' against the expression of drug seeking and 'relapse' and is associated with reductions in GluA1 AMPAR and CAMKIIα levels. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 26 24469593
2014 Apolipoprotein E4 impairs in vivo hippocampal long-term synaptic plasticity by reducing the phosphorylation of CaMKIIα and CREB. Journal of Alzheimer's disease : JAD 24 24787920
2006 Opiate withdrawal induces dynamic expressions of AMPA receptors and its regulatory molecule CaMKIIalpha in hippocampal synapses. Life sciences 23 16616767
2015 CaMKIIα-GluA1 Activity Underlies Vulnerability to Adolescent Binge Alcohol Drinking. Alcoholism, clinical and experimental research 22 26247621
2013 Recombinant probes reveal dynamic localization of CaMKIIα within somata of cortical neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 24005308
2005 Retinal ganglion cell death and neuroprotection: Involvement of the CaMKIIalpha gene. Brain research. Molecular brain research 22 16023257
2020 The effects of lactobacilli (L. rhamnosus, L. reuteri, L. Plantarum) on LPS-induced memory impairment and changes in CaMKII-α and TNF-α genes expression in the hippocampus of rat. Physiology & behavior 21 33127463
2016 Inhibition of CaMKIIα in the Central Nucleus of Amygdala Attenuates Fentanyl-Induced Hyperalgesia in Rats. The Journal of pharmacology and experimental therapeutics 21 27451410
2023 Tilianin improves cognition in a vascular dementia rodent model by targeting miR-193b-3p/CaM- and miR-152-3p/CaMKIIα-mediated inflammatory and apoptotic pathways. Frontiers in immunology 20 37153565
2023 Adnp-mutant mice with cognitive inflexibility, CaMKIIα hyperactivity, and synaptic plasticity deficits. Molecular psychiatry 20 37365244
2021 Treadmill exercise enhances synaptic plasticity in the ischemic penumbra of MCAO mice by inducing the expression of Camk2a via CYFIP1 upregulation. Life sciences 20 33497737
2017 The Effect of Chronic Fluorosis on Calcium Ions and CaMKIIα, and c-fos Expression in the Rat Hippocampus. Biological trace element research 20 28730575
2017 CaMKIIα Expression Defines Two Functionally Distinct Populations of Granule Cells Involved in Different Types of Odor Behavior. Current biology : CB 20 29107547
2015 Opiate Exposure State Controls a D2-CaMKIIα-Dependent Memory Switch in the Amygdala-Prefrontal Cortical Circuit. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 19 26174594
2012 Effects of propofol on the activation of hippocampal CaMKIIα in depressed rats receiving electroconvulsive therapy. The journal of ECT 19 23041766
2017 The protective effects of propofol against CoCl2-induced HT22 cell hypoxia injury via PP2A/CAMKIIα/nNOS pathway. BMC anesthesiology 18 28241801
2014 CaMKIIα and caveolin-1 cooperate to drive ATP-induced membrane delivery of the P2X3 receptor. Journal of molecular cell biology 18 24755854
2013 Large deletions encompassing the TCOF1 and CAMK2A genes are responsible for Treacher Collins syndrome with intellectual disability. European journal of human genetics : EJHG 18 23695276
2017 CaMKIIα Mediates the Effect of IL-17 To Promote Ongoing Spontaneous and Evoked Pain in Multiple Sclerosis. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 29146590
2012 A role for dendritic translation of CaMKIIα mRNA in olfactory plasticity. PloS one 17 22768241
2012 Activity-dependent modulation of the interaction between CaMKIIα and Abi1 and its involvement in spine maturation. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 22993434
2020 Imperatorin ameliorates learning and memory deficits through BDNF/TrkB and ERK/CaMKIIα/CREB signaling in prenatally-stressed female offspring. Phytotherapy research : PTR 16 32281712
2019 Acute Chemogenetic Activation of CamKIIα-Positive Forebrain Excitatory Neurons Regulates Anxiety-Like Behaviour in Mice. Frontiers in behavioral neuroscience 16 31736725
2018 Non-canonical Wnt induces chondrocyte de-differentiation through Frizzled 6 and DVL-2/B-raf/CaMKIIα/syndecan 4 axis. Cell death and differentiation 16 29352270
2017 Non-canonical heterogeneous cellular distribution and co-localization of CaMKIIα and CaMKIIβ in the spinal superficial dorsal horn. Brain structure & function 16 29151114
2024 Natural product Kaji-ichigoside F1 exhibits rapid antidepression via activating the AMPA-BDNF-mTOR pathway and inhibiting the NMDAR-CaMKIIα pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 15 38422650
2021 Characterization of six CaMKIIα variants found in patients with schizophrenia. iScience 15 34667946
2015 L-type calcium channels contribute to 5-HT3-receptor-evoked CaMKIIα and ERK activation and induction of emesis in the least shrew (Cryptotis parva). European journal of pharmacology 15 25748600
2008 Ethanol inhibition of recombinant NMDA receptors is not altered by coexpression of CaMKII-alpha or CaMKII-beta. Alcohol (Fayetteville, N.Y.) 15 18562151
2022 CaMKIIα Signaling Is Required for the Neuroprotective Effects of Dl-3-n-Butylphthalide in Alzheimer's Disease. Molecular neurobiology 14 35305243
2020 Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes. Virulence 14 31957543
2019 Icariin ameliorates learning and memory impairments through ERK/CaMKIIα/CREB signaling and HPA axis in prenatally stressed female offspring. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 14 31177064
2017 CaMKIIα may modulate fentanyl-induced hyperalgesia via a CeLC-PAG-RVM-spinal cord descending facilitative pain pathway in rats. PloS one 14 28489932
2012 Bi-directional regulation of CaMKIIα phosphorylation at Thr286 by NMDA receptors in cultured cortical neurons. Journal of neurochemistry 14 22582824
2021 Chemogenetic inhibition of ventral hippocampal CaMKIIα-expressing neurons attenuates anxiety- but not fear-like defensive behaviors in male Long-Evans hooded rats. Neuroscience letters 13 33647396
2020 Regular Aerobic Exercise-Alleviated Dysregulation of CAMKIIα Carbonylation to Mitigate Parkinsonism via Homeostasis of Apoptosis With Autophagy. Journal of neuropathology and experimental neurology 13 31750928
2016 CaMKIIα knockdown decreases anxiety in the open field and low serotonin-induced upregulation of GluA1 in the basolateral amygdala. Behavioural brain research 13 26821292
2015 Fragile X Syndrome FMRP Co-localizes with Regulatory Targets PSD-95, GABA Receptors, CaMKIIα, and mGluR5 at Fiber Cell Membranes in the Eye Lens. Neurochemical research 13 26298628
2024 SIRT1 mediates the excitability of spinal CaMKIIα-positive neurons and participates in neuropathic pain by controlling Nav1.3. CNS neuroscience & therapeutics 12 38828629
2023 Antidepressant effects of repeated s-ketamine administration as NMDAR Antagonist: Involvement of CaMKIIα and mTOR signaling in the hippocampus of CUMS mice. Brain research 12 37146745
2022 MicroRNA-3200-3p targeting CAMK2A modulates the proliferation and metastasis of glioma in vitro. Bioengineered 12 35287547
2021 Effects of N-Methyl-D-aspartate receptor (NMDAR) and Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) on learning and memory impairment in depressed rats with different charge by modified electroconvulsive shock. Annals of translational medicine 12 34532457
2019 SK Channel Modulates Synaptic Plasticity by Tuning CaMKIIα/β Dynamics. Frontiers in synaptic neuroscience 12 31736736
2015 Camk2a-Cre-mediated conditional deletion of chromatin remodeler Brg1 causes perinatal hydrocephalus. Neuroscience letters 12 25929186
2024 circADAMTS6 via stabilizing CAMK2A is involved in smoking-induced emphysema through driving M2 macrophage polarization. Environment international 11 38936066
2023 The GHB analogue HOCPCA improves deficits in cognition and sensorimotor function after MCAO via CaMKIIα. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 11 37026450
2022 Exploring the NCS-382 Scaffold for CaMKIIα Modulation: Synthesis, Biochemical Pharmacology, and Biophysical Characterization of Ph-HTBA as a Novel High-Affinity Brain-Penetrant Stabilizer of the CaMKIIα Hub Domain. Journal of medicinal chemistry 11 36346645
2018 Activated CaMKIIα Binds to the mGlu5 Metabotropic Glutamate Receptor and Modulates Calcium Mobilization. Molecular pharmacology 11 30282777

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