Affinage

CACNG2

Voltage-dependent calcium channel gamma-2 subunit · UniProt Q9Y698

Length
323 aa
Mass
36.0 kDa
Annotated
2026-06-09
89 papers in source corpus 43 papers cited in narrative 40 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

Stargazin (CACNG2) is an obligate auxiliary (TARP) subunit of native neuronal AMPA receptor complexes that couples receptor surface delivery, synaptic anchoring, and channel gating into one regulated system (PMID:11140673, PMID:15630087). It acts through two structurally and functionally separable modules: an extracellular/transmembrane interface that allosterically tunes channel behavior, and a cytoplasmic tail that directs trafficking and synaptic localization (PMID:15858532, PMID:16793768). Through its membrane-domain contacts with neighboring AMPAR subunits (M1/M4) and its own TM3/TM4 and extracellular loop 2, stargazin destabilizes the closed channel state and stabilizes the activated/open state, slowing deactivation and desensitization, accelerating recovery, and promoting closure of the ligand-binding domain (PMID:15758178, PMID:16093395, PMID:15567474, PMID:28238551, PMID:25422502); cryo-EM and single-molecule energy-transfer studies place stargazin beneath the AMPAR ligand-binding domain with conserved electrostatic interfaces and variable stoichiometry, supporting a conformational-selection model favoring the activated state (PMID:27365450, PMID:27705782). It additionally relieves intracellular polyamine block of calcium-permeable AMPARs and shapes responses to declining synaptic glutamate, with these effects selective for AMPA over kainate receptors (PMID:17873873, PMID:28919175, PMID:12920207). The cytoplasmic tail binds the first two PDZ domains of PSD-95, trapping diffusing AMPAR–stargazin complexes at synapses and setting synaptic AMPAR number; disrupting this interaction increases receptor surface diffusion and prevents postsynaptic accumulation (PMID:12359873, PMID:17329211). Glutamate binding allosterically dissociates AMPARs from stargazin, and desensitized receptors bind stargazin more weakly and become more mobile, linking receptor conformational state to synaptic stabilization (PMID:15001777, PMID:25661182). Stargazin phosphorylation controls bidirectional plasticity: CaMKII/PKC phosphorylation and PKA phosphorylation at Thr-321 promote synaptic trapping and AMPAR insertion, while MAPK phosphorylation and PP1/PP2B-mediated dephosphorylation drive removal; phosphorylation extends the tail to engage higher-affinity deep PDZ domains of PSD-95, and PKA phosphorylation of Thr-321 within the PDZ-binding motif disrupts the PSD-95 interaction (PMID:12122038, PMID:11805122, PMID:15664178, PMID:20670832, PMID:25843401, PMID:19968761). In its dephosphorylated state, stargazin recruits AP-2 and AP-3A adaptors to drive NMDA-induced endocytosis, lysosomal routing, and homeostatic downscaling underlying LTD (PMID:24217640, PMID:30271322). The intellectual-disability-associated V143L mutation weakens the AMPAR:stargazin interface and produces impaired spine maturation, deficient CA1 LTP, and cognitive/social deficits in knock-in mice (PMID:35256745).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2000 High

    Established stargazin as a dual-function AMPAR partner, resolving how a single auxiliary protein could both deliver receptors to the surface and target them to synapses.

    Evidence Co-IP plus transfection rescue in stargazer granule cells and PDZ-binding mutant expression in pyramidal cells

    PMID:11140673

    Open questions at the time
    • Did not define the structural interface of the ectodomain–AMPAR interaction
    • Did not establish stoichiometry or gating consequences
  2. 2002 High

    Showed that direct stargazin–PSD-95 PDZ binding quantitatively sets synaptic AMPAR number and that PKA phosphorylation at Thr-321 disrupts this interaction, defining a tunable molecular switch for synaptic strength.

    Evidence Compensatory PDZ/PDZ-motif mutagenesis with electrophysiology, plus in vitro kinase assay, phospho-specific antibodies and neuronal readouts

    PMID:11805122 PMID:12122038 PMID:12359873

    Open questions at the time
    • Did not resolve the dynamics of complex trapping versus diffusion
    • Did not identify the upstream signals coupling activity to PKA phosphorylation in vivo
  3. 2004 Medium

    Demonstrated that glutamate binding allosterically dissociates AMPARs from a membrane-stable stargazin pool, linking receptor activation to internalization independently of ion flux.

    Evidence Surface biotinylation, Co-IP and glutamate stimulation in heterologous cells and neurons

    PMID:15001777

    Open questions at the time
    • Single lab
    • Did not establish whether dissociation is required for endocytosis in vivo
  4. 2005 High

    Separated stargazin's two mechanisms anatomically — ectodomain controls gating (slowed deactivation/desensitization) while the cytoplasmic tail controls trafficking — and confirmed it is a native AMPAR complex subunit required for bidirectional plasticity.

    Evidence Domain swaps and mutagenesis with oocyte/HEK and slice electrophysiology, blue native gels of cerebellar complexes, kinase/phosphatase manipulation of LTP/LTD

    PMID:15567474 PMID:15630087 PMID:15664178 PMID:15758178 PMID:15858532 PMID:16093395

    Open questions at the time
    • Did not provide atomic-resolution view of the gating interface
    • Did not map all phosphorylation sites to specific plasticity outcomes
  5. 2007 High

    Established that the stargazin–PSD-95 interaction works by trapping laterally diffusing AMPAR–stargazin complexes and that stargazin relieves polyamine block of calcium-permeable AMPARs, connecting molecular interactions to receptor mobility and biophysics.

    Evidence Single quantum-dot tracking and FRAP with dominant-negative stargazin; polyamine block analysis in heterologous and stellate cells

    PMID:17329211 PMID:17873873

    Open questions at the time
    • Did not resolve how phosphorylation state alters trapping kinetics
    • Polyamine effect mechanism at the structural level undefined
  6. 2010 High

    Demonstrated that CaMKII activation triggers synaptic AMPAR trapping specifically through stargazin phosphorylation and PDZ scaffold binding, identifying stargazin rather than GluA1 as the phosphorylation substrate for plasticity-driven immobilization.

    Evidence Single-particle tracking with CaMKII manipulation, phosphomimetic/null stargazin mutants, short-term plasticity electrophysiology

    PMID:20670832

    Open questions at the time
    • Did not quantify contribution of individual phospho-sites
    • Did not address other TARP family members in the same pathway
  7. 2013 High

    Identified phosphorylation-state-dependent stargazin–AP-2 and stargazin–AP-3A complexes as the machinery for NMDA-induced endocytosis and lysosomal routing, completing the removal arm of plasticity.

    Evidence Co-IP, competitive disruption peptides and LTD electrophysiology in hippocampal neurons

    PMID:24217640

    Open questions at the time
    • Single lab for the dual-adaptor model
    • Did not resolve the structural basis of phospho-dependent adaptor selectivity
  8. 2015 High

    Showed that AMPAR conformational state controls stargazin affinity — desensitized receptors bind less stargazin and become more mobile — and that tail lengthening by phosphorylation engages higher-affinity deep PSD-95 PDZ domains, mechanistically coupling gating to anchoring.

    Evidence Single-molecule tracking with conformational-state stabilization; artificial linker insertion and phosphomimetics with synaptic electrophysiology

    PMID:25661182 PMID:25843401

    Open questions at the time
    • Deep-PDZ model from a single lab
    • Did not measure in vivo tail extension dynamics
  9. 2016 High

    Provided direct structural mechanism: cryo-EM and energy-transfer studies positioned stargazin below the ligand-binding domain with conserved electrostatic interfaces and variable stoichiometry, supporting a conformational-selection model for activated-state stabilization.

    Evidence Cryo-EM of AMPAR–stargazin complexes; LRET/smFRET in HEK293 cells

    PMID:27365450 PMID:27705782

    Open questions at the time
    • Functional consequence of one-versus-two stargazin stoichiometry unresolved
    • Cytoplasmic tail interactions not visualized
  10. 2017 High

    Delineated the molecular interface as AMPAR M1/M4 contacts initiated by the C-tail plus TARP TM3/TM4 and extracellular loop 2, with a two-step gating mechanism (destabilize closed state, then stabilize activated state).

    Evidence Systematic stargazin/GluK2 domain swaps and TARP chimeras with electrophysiology

    PMID:28238551

    Open questions at the time
    • Did not assign individual residues to each step
    • Did not address tail-dependent trafficking in the same assay
  11. 2022 Medium

    Connected stargazin dysfunction to human disease by showing that the V143L mutation weakens the AMPAR:stargazin interface and causes synaptic, plasticity, and behavioral deficits in knock-in mice.

    Evidence Molecular dynamics, knock-in mouse with spine imaging, patch-clamp electrophysiology and behavioral testing

    PMID:35256745

    Open questions at the time
    • Single lab
    • Causal link from interface weakening to specific behavioral phenotypes not fully dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the full repertoire of post-translational modifications (phosphorylation, S-nitrosylation, calpain cleavage) is integrated in vivo to set AMPAR surface levels, and how non-AMPAR functions (CaV2.2/Gβγ modulation, serine racemase regulation) contribute physiologically, remains unresolved.
  • S-nitrosylation and calpain regulation rest on single-lab evidence
  • Non-AMPAR roles (CaV2.2, serine racemase, nPIST, LC2, MAGI-2) not integrated into a unified physiological model

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0005198 structural molecule activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-9609507 Protein localization 4
Partners
AP2AP3DLG4GOPCGRIA1GRIA2MAGI2SRR
Complex memberships
AMPA receptor–TARP complexAMPAR–stargazin–PSD-95 complex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Stargazin interacts with AMPA receptor subunits (required for surface membrane delivery) and with synaptic PDZ proteins such as PSD-95 via a C-terminal PDZ-binding domain (required for synaptic targeting). These are two distinct mechanisms: ectodomain–AMPAR interaction for surface delivery, and C-terminal PDZ-binding for synaptic localization. Co-immunoprecipitation, transfection rescue in stargazer cerebellar granule cells, expression of PDZ-binding domain mutant in hippocampal pyramidal cells Nature High 11140673
2002 Direct binding of the first two PDZ domains of PSD-95 to stargazin controls the number of synaptic AMPARs. Increasing PSD-95 recruits new AMPARs to synapses without changing total surface AMPARs; stargazin overexpression increases extrasynaptic AMPARs but not synaptic currents when PSD-95 is held constant. Compensatory mutations in both PSD-95 and stargazin confirmed the direct interaction is the determinant of synaptic AMPAR number. Biolistic transfection in hippocampal slice cultures, compensatory mutagenesis of PSD-95 PDZ domains and stargazin PDZ-binding motif, electrophysiology Proceedings of the National Academy of Sciences of the United States of America High 12359873
2002 PKA phosphorylates stargazin at Thr-321 within the C-terminal PDZ-binding motif, disrupting its interaction with PSD-95 and reducing synaptic AMPAR function. A phosphomimetic T321E mutation abolishes stargazin–PSD-95 co-clustering and downregulates synaptic AMPARs in hippocampal neurons. In vitro peptide phosphorylation assay, phospho-specific antibodies, yeast two-hybrid, co-immunoprecipitation, COS-7 and hippocampal neuron transfections The Journal of neuroscience High 11805122 12122038
2004 TARPs (including stargazin) are stable at the plasma membrane while AMPA receptors cycle; upon glutamate binding, AMPA receptors dissociate from stargazin by an allosteric mechanism that does not require ion flux or intracellular second messengers, and this dissociation may participate in glutamate-mediated receptor internalization. Surface biotinylation, co-immunoprecipitation, glutamate stimulation assays in heterologous cells and neurons Science Medium 15001777
2005 Stargazin's ectodomain controls AMPA receptor channel gating (slows deactivation and desensitization, increases channel opening rate), while its cytoplasmic tail determines receptor trafficking. Disrupting the stargazin ectodomain–AMPAR interaction alters the amplitude and shape of synaptic responses. Mutagenesis, electrophysiology in Xenopus oocytes and HEK cells, hippocampal slice recording Nature High 15858532
2005 Stargazin reduces AMPA receptor desensitization and slows deactivation when co-expressed in Xenopus oocytes or HEK293 cells, acting as a positive allosteric modulator that stabilizes the receptor conformation and accelerates recovery from desensitization. Electrophysiology in Xenopus oocytes and HEK293 cells, co-expression studies The Journal of neuroscience High 15567474 15758178 16093395
2005 Stargazin phosphorylation by CaMKII and PKC promotes synaptic AMPAR trafficking (LTP), while dephosphorylation by PP1 (downstream of PP2B) mediates LTD. Stargazin is quantitatively phosphorylated at multiple sites and is required for bidirectional synaptic plasticity at hippocampal synapses. Phosphorylation assays, mutagenesis, hippocampal slice LTP/LTD electrophysiology, pharmacological manipulation of kinases and phosphatases Neuron High 15664178
2005 Stargazin is an auxiliary subunit of native AMPA receptor complexes in the cerebellum; blue native gel electrophoresis identifies two AMPAR populations — one containing stargazin and one lacking it. Other AMPAR-interacting proteins (SAP97, GRIP1, PICK1, NSF, AP2, 4.1N) do not significantly associate with AMPARs on native gels. Blue native gel electrophoresis of cerebellar extracts, limited proteolysis, co-immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America High 15630087
2005 Stargazin promotes biosynthetic transport of AMPA receptors through the ER; its effect is mimicked and occluded by upregulation of ER chaperones (UPR), and UPR induction is detected in cerebellar granule cells lacking stargazin, indicating a role in ER processing. COS7 cell transfection, dominant-negative dynamin mutant, UPR assays, pharmacological UPR inhibition in stargazin-deficient neurons The Journal of neuroscience Medium 15689545
2006 Stargazin controls AMPA receptor potentiator pharmacology: it makes both flip and flop splice forms of GluR1 sensitive to both cyclothiazide and PEPA, and enhances the effect of AMPAR potentiators on channel deactivation. Electrophysiology in heterologous cells co-expressing GluR1 splice variants and stargazin, with AMPAR potentiator pharmacology Proceedings of the National Academy of Sciences of the United States of America Medium 16785437
2006 Stargazin interacts functionally with the glutamate-binding domain of GluR1: a Lurcher-equivalent point mutation in the GluR1 ligand-binding domain abolishes stargazin's effects on both trafficking and gating, while a mutation preventing desensitization modulates gating effects but preserves trafficking. Site-directed mutagenesis of GluR1, co-expression with stargazin in heterologous cells, electrophysiology and surface expression assays Neuropharmacology Medium 16919685
2006 Stargazin binds MAGI-2 (a multi-PDZ scaffolding protein) via its C-terminal -TTPV motif through MAGI-2's PDZ1, PDZ3, and PDZ5 domains; this interaction was confirmed by co-immunoprecipitation from mouse cerebral cortex and in vitro binding assays. Yeast two-hybrid screening, co-immunoprecipitation from mouse brain, in vitro binding assays, HEK-293T transfection The Journal of neuroscience Medium 16870733
2007 The stargazin–PSD-95 interaction controls AMPA receptor lateral diffusion and synaptic trapping. Disruption of the stargazin–PSD-95 interaction strongly increases AMPAR surface diffusion, preventing AMPAR accumulation at postsynaptic sites. AMPARs and stargazin diffuse as complexes into and out of synapses. Single quantum dot tracking and FRAP imaging in live hippocampal neurons, dominant-negative stargazin constructs Neuron High 17329211
2007 Stargazin greatly reduces block of calcium-permeable AMPARs by intracellular polyamines, decreasing CP-AMPAR affinity for cytoplasmic polyamines, enhancing charge transfer after single glutamate applications, and eliminating frequency-dependent facilitation. Electrophysiology in heterologous cells and cerebellar stellate cells, polyamine block analysis Nature neuroscience High 17873873
2004 Stargazin interacts with nPIST (a Golgi-enriched PDZ protein) through a novel cytoplasmic domain (residues 243–283). nPIST overexpression enhances and dominant-negative nPIST attenuates AMPAR synaptic clustering, identifying a role for stargazin–nPIST interaction in AMPAR trafficking to the synapse. Yeast two-hybrid, co-immunoprecipitation from brain, immunohistochemistry, transfection in hippocampal neurons The Journal of neuroscience Medium 15329396
2004 Microtubule-associated protein light chain 2 (LC2) directly interacts with the intracellular C-terminal tail of stargazin upstream of the -TTPV sequence, and forms a tripartite complex with stargazin and GluR2 in cerebellar neurons, suggesting a role in pre-synaptic AMPAR trafficking before synaptic anchoring. Yeast two-hybrid, immunoprecipitation of cerebellar extracts, native stargazin immunopurification The Journal of biological chemistry Medium 15136571
2009 Stargazin is physiologically S-nitrosylated; S-nitrosylation increases its binding to GluR1 AMPAR subunit and causes increased surface expression of AMPARs. NMDAR stimulation activates nNOS, which increases stargazin nitrosylation and GluR1 binding. Biotin switch assay for S-nitrosylation, co-immunoprecipitation, surface biotinylation in heterologous cells and primary neurons Proceedings of the National Academy of Sciences of the United States of America Medium 19805317
2010 CaMKII activation and postsynaptic translocation triggers synaptic trapping of AMPARs via phosphorylation of stargazin and its binding to PDZ domain scaffolds. AMPAR immobilization requires both stargazin phosphorylation and PDZ scaffold binding, but not GluA1 PDZ-binding domain or GluA1-Ser831 phosphorylation. Single-particle tracking of AMPARs in hippocampal neurons, CaMKII activation/inhibition, phosphomimetic/phospho-null stargazin mutants, short-term plasticity electrophysiology Neuron High 20670832
2013 Stargazin forms ternary complexes with AP-2 and AP-3A adaptor proteins in a phosphorylation-state-dependent manner. Stargazin–AP-2 interaction is required for NMDA-induced AMPAR endocytosis, while stargazin–AP-3A interaction is required for late endosomal/lysosomal trafficking, preventing receptor recycling. Both interactions are necessary for LTD at CA1 synapses. Co-immunoprecipitation in hippocampal neurons, competitive peptide inhibitors, LTD electrophysiology, receptor trafficking assays Nature communications High 24217640
2015 Desensitized AMPARs bind less stargazin and are less stabilized at the synapse compared to open or closed-resting state receptors. Glutamate-induced AMPAR desensitization increases AMPAR mobility within the synapse, and this mobility-mediated short-term plasticity regulation is abolished when the glutamate-dependent loss in AMPAR–stargazin interaction is prevented. Single-molecule AMPAR tracking, point mutations and pharmacology to stabilize AMPAR conformational states, synaptic electrophysiology Neuron High 25661182
2015 Phosphorylation-induced extension or artificial lengthening of the stargazin cytoplasmic tail enhances its binding to the deeper (farther from membrane) PDZ domains of PSD-95, which have higher affinity for the stargazin PDZ-binding motif, thereby potentiating AMPAR anchoring and synaptic transmission. Artificial linker insertion, phosphomimetic mutations, single-molecule tracking, synaptic electrophysiology in hippocampal neurons Neuron Medium 25843401
2016 Cryo-EM structures of AMPAR–stargazin complexes reveal variable stoichiometry (one or two stargazin molecules per tetrameric AMPAR) and electrostatic interactions between the extracellular domains of AMPAR and stargazin that are conserved across AMPARs and TARPs. The structures support a model where TARPs stabilize the activated state of AMPARs. Cryo-electron microscopy, structural analysis of AMPAR–STZ complexes Science High 27365450
2016 Single-molecule LRET and smFRET show that stargazin is positioned below the AMPAR ligand-binding domain and acts as a scaffold to stabilize or select AMPAR conformational states that favor activation (conformational selection model). Luminescence resonance energy transfer (LRET), single-molecule FRET (smFRET) in HEK293 cells Cell reports Medium 27705782
2017 Stargazin primarily interacts with AMPAR via membrane domains M1 and M4 of neighboring AMPAR subunits, initiated/stabilized by the AMPAR C-tail. TARP TM3, TM4, and extracellular loop 2 are also key contributors. Mechanistically, TARP binding destabilizes the channel closed state (two-step action: binding destabilizes closed state, enabling efficient opening; activated state is then stabilized via subsequent interactions). Systematic domain swaps between stargazin and TARP-insensitive GluK2 kainate receptor, TARP chimeras, electrophysiology in heterologous cells Neuron High 28238551
2017 Stargazin and cornichon 3 (CNIH3) share a lipid-exposed transmembrane domain surface on GluA2 (including A793 and C528 residues) for their function, but induce opposing gating effects through this shared surface. Both extracellular and TMD elements contribute independently to gating modulation by stargazin. TMD mutagenesis of GluA2, detergent stability assays, electrophysiology, cryo-EM structure comparison The Journal of physiology Medium 28815591
2014 Stargazin promotes closure of the AMPAR ligand-binding domain (LBD): it rescues gating deficits of LBD-destabilizing mutations, reduces NBQX accessibility, and LRET measurements directly show the LBD is on average more closed in both apo and agonist-bound states in the presence of stargazin. Mutagenesis of AMPAR LBD, LRET measurements, accessibility assays with NBQX, electrophysiology The Journal of general physiology Medium 25422502
2009 Stargazin phosphorylation protects GluR1 from lysosomal degradation and increases dendritic GluR1 levels, but does not increase surface or synaptic GluR1 levels. Stargazin does not protect GluR2 from lysosomal degradation. Viral expression of AMPAR subunits with/without stargazin in rat hippocampal neurons, lysosomal inhibition, surface biotinylation, electrophysiology Nature neuroscience Medium 19543281
2009 Stargazin T321 is phosphorylated by both PKA and MAPKs. PKA phosphorylation of T321 is required for activity-dependent increases in stargazin synaptic clustering, while MAPK phosphorylation of T321 is required for activity-dependent decreases in synaptic clustering, thus controlling bidirectional synaptic plasticity. Point mutations blocking PKA- or MAPK-specific T321 phosphorylation, activity stimulation in dissociated hippocampal neurons, immunofluorescence clustering assays Journal of neurochemistry Medium 19968761
2003 Stargazin action on surface delivery is highly selective for AMPA receptors; surface delivery of kainate receptors is independent of stargazin in cerebellar granule cells and Xenopus oocytes. Electrophysiology in cerebellar granule cells and Xenopus oocytes, co-expression of kainate receptor subunits with stargazin Molecular pharmacology Medium 12920207
2010 Stargazin modulates CaV2.2 (N-type) channels via a Gβγ-dependent mechanism: the cytoplasmic C-terminus of stargazin binds Gβγ in vitro and counteracts Gβγ-induced inhibition of CaV2.2 and Gβγ-mediated GIRK activation. Effects on channel biophysical properties are not through direct modulation of the channel itself. Co-expression in Xenopus oocytes, Gβγ scavenger proteins, in vitro pull-down of Gβγ by stargazin C-terminus The Journal of biological chemistry Medium 20435886
2011 Stargazin in cerebellar stellate cells is required for synaptic (but not extrasynaptic) AMPAR trafficking, and for activity-dependent plasticity of synaptic AMPAR rectification at parallel fiber–stellate cell synapses. Electrophysiology in stargazer mutant mice and wild-type controls, philanthotoxin-433 block, rectification index measurements The Journal of neuroscience Medium 21411637
2011 Calpain activation cleaves/truncates stargazin in rat brain, producing decreased stargazin immunoreactivity in the neuropil, suggesting calpain-mediated regulation of AMPAR targeting through stargazin truncation. Calcium treatment of brain sections, calpain inhibitor, immunocytochemistry, Western blot Neuroscience Low 21256931
2014 Serine racemase (SR) forms a ternary complex with PSD-95 and stargazin; SR binds stargazin C-terminus, which facilitates SR membrane localization and inhibits SR activity. AMPA receptor activation internalizes SR and disrupts stargazin–SR interaction, derepressing SR activity and increasing D-serine production, potentially coupling AMPA and NMDA receptor activities. Co-immunoprecipitation, enzyme activity assays, subcellular fractionation, AMPAR stimulation in neurons The Journal of biological chemistry Medium 25164819
2004 Stargazin links synaptic AMPA and NMDA receptors: synaptic targeting of NMDA receptors in ventral spinal neurons and hippocampal interneurons is dependent on the presence of synaptic AMPARs, with AMPA and NMDA receptors linked by stargazin and a MAGUK protein. Transfection of NR2A/B into spinal neurons, dominant-negative GluR2 mutants, AMPAR/NMDAR clustering assays Neuron Medium 15473971
2018 Stargazin dephosphorylation during homeostatic synaptic downscaling increases stargazin surface mobility and GluA1-AMPAR mobility at synaptic sites. Stargazin dephosphorylation mediates interaction with AP-2 and AP-3A to promote AMPAR endocytosis and lysosomal degradation; disruption of stargazin–AP-3A interaction prevents GluA1 surface decrease during chronic activity elevation. Single-molecule tracking, competitive peptide inhibitors for AP-2 and AP-3A, surface biotinylation, chronic activity manipulation in cortical neurons Frontiers in molecular neuroscience Medium 30271322
2019 Stargazin (γ-2) slows both channel opening (kop) and closing (kcl) rates of GluA4 homomeric channels by approximately 4-fold and 3-fold, respectively, without appreciable change in channel-opening probability, lengthening the lifetime of open channels and allowing larger charge transfer. Laser-pulse photolysis technique with rapid glutamate application, single-channel kinetic analysis Scientific reports Medium 31267004
2017 Stargazin enhances the AMPAR response to low concentrations of glutamate; at the cerebellar mossy fiber–unipolar brush cell synapse, recovery from AMPAR desensitization during slow EPSCs is mediated by stargazin enabling receptor responses to declining synaptic glutamate levels. Electrophysiology at identified cerebellar synapses, pharmacological manipulation of AMPAR desensitization and glutamate transporters Neuron Medium 28919175
2007 The C-terminal cytoplasmic tail of stargazin encodes an intrinsic and transferable membrane sorting signal; fusing it to heterologous receptors (GluR1 or GnRH receptor) promotes ER exit and basolateral membrane sorting. Chimeric receptor constructs, confocal imaging of membrane sorting in transfected cells The Journal of biological chemistry Low 17986442
2005 Stargazin-mediated trafficking to the plasma membrane and its modulation of AMPAR gating/desensitization are separable functions requiring different AMPAR domains: the cytoplasmic domain is required for trafficking (FRET interaction in ER) but not for desensitization modulation. FRET between fluorophore-tagged GluR1/GluR2 and stargazin, confocal surface expression imaging, electrophysiology in HEK cells The Journal of biological chemistry Medium 16793768
2022 The intellectual disability-associated stargazin V143L mutation weakens the AMPAR:stargazin complex interface (predicted by molecular dynamics), and knock-in mice exhibit impaired spine maturation, abnormal synaptic transmission, impaired LTP specifically in basal dendrites of CA1 neurons, and cognitive/social deficits. Molecular dynamics simulations, knock-in mouse model, dendritic spine imaging, patch-clamp electrophysiology, behavioral testing Molecular psychiatry Medium 35256745

Source papers

Stage 0 corpus · 89 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature 892 11140673
2002 Direct interactions between PSD-95 and stargazin control synaptic AMPA receptor number. Proceedings of the National Academy of Sciences of the United States of America 614 12359873
2007 The interaction between Stargazin and PSD-95 regulates AMPA receptor surface trafficking. Neuron 459 17329211
2005 Stargazin modulates AMPA receptor gating and trafficking by distinct domains. Nature 398 15858532
2010 CaMKII triggers the diffusional trapping of surface AMPARs through phosphorylation of stargazin. Neuron 321 20670832
2005 Bidirectional synaptic plasticity regulated by phosphorylation of stargazin-like TARPs. Neuron 263 15664178
2005 Stargazin reduces desensitization and slows deactivation of the AMPA-type glutamate receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 213 15758178
2004 Dynamic interaction of stargazin-like TARPs with cycling AMPA receptors at synapses. Science (New York, N.Y.) 189 15001777
2007 Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors. Nature neuroscience 155 17873873
2005 Stargazin modulates native AMPA receptor functional properties by two distinct mechanisms. The Journal of neuroscience : the official journal of the Society for Neuroscience 147 16093395
2005 Stargazin is an AMPA receptor auxiliary subunit. Proceedings of the National Academy of Sciences of the United States of America 133 15630087
2002 Phosphorylation of the postsynaptic density-95 (PSD-95)/discs large/zona occludens-1 binding site of stargazin regulates binding to PSD-95 and synaptic targeting of AMPA receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 127 12122038
2016 Elucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy. Science (New York, N.Y.) 123 27365450
2015 Glutamate-induced AMPA receptor desensitization increases their mobility and modulates short-term plasticity through unbinding from Stargazin. Neuron 117 25661182
2010 Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2. Genome research 107 20688780
2002 Phosphorylation of stargazin by protein kinase A regulates its interaction with PSD-95. The Journal of biological chemistry 106 11805122
2005 Interaction with the unfolded protein response reveals a role for stargazin in biosynthetic AMPA receptor transport. The Journal of neuroscience : the official journal of the Society for Neuroscience 96 15689545
2009 Roles of stargazin and phosphorylation in the control of AMPA receptor subcellular distribution. Nature neuroscience 83 19543281
2015 Lengthening of the Stargazin Cytoplasmic Tail Increases Synaptic Transmission by Promoting Interaction to Deeper Domains of PSD-95. Neuron 76 25843401
2004 A novel action of stargazin as an enhancer of AMPA receptor activity. Neuroscience research 74 15567474
2002 The novel product of a five-exon stargazin-related gene abolishes Ca(V)2.2 calcium channel expression. The EMBO journal 67 11927536
2013 Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression. Nature communications 66 24217640
2006 Stargazin and other transmembrane AMPA receptor regulating proteins interact with synaptic scaffolding protein MAGI-2 in brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 65 16870733
2004 AMPA receptor synaptic targeting regulated by stargazin interactions with the Golgi-resident PDZ protein nPIST. The Journal of neuroscience : the official journal of the Society for Neuroscience 63 15329396
2009 S-nitrosylation of stargazin regulates surface expression of AMPA-glutamate neurotransmitter receptors. Proceedings of the National Academy of Sciences of the United States of America 62 19805317
2006 Stargazin controls the pharmacology of AMPA receptor potentiators. Proceedings of the National Academy of Sciences of the United States of America 60 16785437
2003 Stargazin differentially controls the trafficking of alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate and kainate receptors. Molecular pharmacology 60 12920207
2010 Contribution of the global subunit structure and stargazin on the maturation of AMPA receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 20164357
2006 Stargazin interacts functionally with the AMPA receptor glutamate-binding module. Neuropharmacology 55 16919685
2006 Different domains of the AMPA receptor direct stargazin-mediated trafficking and stargazin-mediated modulation of kinetics. The Journal of biological chemistry 53 16793768
2006 Reconstitution of invertebrate glutamate receptor function depends on stargazin-like proteins. Proceedings of the National Academy of Sciences of the United States of America 53 16818877
2016 Stargazin Modulation of AMPA Receptors. Cell reports 52 27705782
2011 Stargazin (TARP gamma-2) is required for compartment-specific AMPA receptor trafficking and synaptic plasticity in cerebellar stellate cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 51 21411637
2006 Learning from stargazin: the mouse, the phenotype and the unexpected. Current opinion in neurobiology 51 16678401
2008 RASD2, MYH9, and CACNG2 genes at chromosome 22q12 associated with the subgroup of schizophrenia with non-deficit in sustained attention and executive function. Biological psychiatry 49 18571626
2017 Molecular Mechanism of AMPA Receptor Modulation by TARP/Stargazin. Neuron 48 28238551
2006 Differential localization and regulation of stargazin-like protein, gamma-8 and stargazin in the plasma membrane of hippocampal and cortical neurons. Neuroscience research 46 16516319
2007 The transmembrane AMPA receptor regulatory protein gamma 4 is a more effective modulator of AMPA receptor function than stargazin (gamma 2). The Journal of neuroscience : the official journal of the Society for Neuroscience 45 17670991
2014 A role for stargazin in experience-dependent plasticity. Cell reports 44 24882000
2014 Stargazin promotes closure of the AMPA receptor ligand-binding domain. The Journal of general physiology 42 25422502
2007 AMPA receptors and stargazin-like transmembrane AMPA receptor-regulatory proteins mediate hippocampal kainate neurotoxicity. Proceedings of the National Academy of Sciences of the United States of America 40 18000041
2005 The alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptor trafficking regulator "stargazin" is related to the claudin family of proteins by Its ability to mediate cell-cell adhesion. The Journal of biological chemistry 40 15760900
2006 Three-dimensional structure of an AMPA receptor without associated stargazin/TARP proteins. Biological chemistry 39 16497150
2003 Human neuronal stargazin-like proteins, gamma2, gamma3 and gamma4; an investigation of their specific localization in human brain and their influence on CaV2.1 voltage-dependent calcium channels expressed in Xenopus oocytes. BMC neuroscience 37 14505496
2014 Serine racemase regulated by binding to stargazin and PSD-95: potential N-methyl-D-aspartate-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (NMDA-AMPA) glutamate neurotransmission cross-talk. The Journal of biological chemistry 36 25164819
2008 Stargazin modulates AMPA receptor antagonism. Neuropharmacology 34 18378265
2008 The stargazin-related protein gamma 7 interacts with the mRNA-binding protein heterogeneous nuclear ribonucleoprotein A2 and regulates the stability of specific mRNAs, including CaV2.2. The Journal of neuroscience : the official journal of the Society for Neuroscience 33 18923037
2004 AMPA receptor-dependent clustering of synaptic NMDA receptors is mediated by Stargazin and NR2A/B in spinal neurons and hippocampal interneurons. Neuron 33 15473971
2017 Engineering defined membrane-embedded elements of AMPA receptor induces opposing gating modulation by cornichon 3 and stargazin. The Journal of physiology 32 28815591
2004 Microtubule-associated protein light chain 2 is a stargazin-AMPA receptor complex-interacting protein in vivo. The Journal of biological chemistry 31 15136571
2008 Stargazin involvement with bipolar disorder and response to lithium treatment. Pharmacogenetics and genomics 30 18408563
2005 A targeted mutation in Cacng4 exacerbates spike-wave seizures in stargazer (Cacng2) mice. Proceedings of the National Academy of Sciences of the United States of America 30 15677329
2017 Slow AMPAR Synaptic Transmission Is Determined by Stargazin and Glutamate Transporters. Neuron 25 28919175
2011 Stargazin and AMPA receptor membrane expression is increased in the somatosensory cortex of Genetic Absence Epilepsy Rats from Strasbourg. Neurobiology of disease 24 21220022
2006 New role for spinal Stargazin in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated pain sensitization after inflammation. Journal of neuroscience research 21 16791853
2009 Regulation of stargazin synaptic trafficking by C-terminal PDZ ligand phosphorylation in bidirectional synaptic plasticity. Journal of neurochemistry 20 19968761
2007 The stargazin C terminus encodes an intrinsic and transferable membrane sorting signal. The Journal of biological chemistry 20 17986442
2003 Phenotypic heterogeneity in the stargazin allelic series. Mammalian genome : official journal of the International Mammalian Genome Society 20 12925883
2014 Down-regulation of Stargazin inhibits the enhanced surface delivery of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor GluR1 subunit in rat dorsal horn and ameliorates postoperative pain. Anesthesiology 19 25093662
2013 AMPA receptor upregulation in the nucleus accumbens shell of cocaine-sensitized rats depends upon S-nitrosylation of stargazin. Neuropharmacology 19 24035918
2010 Stargazin modulates neuronal voltage-dependent Ca(2+) channel Ca(v)2.2 by a Gbetagamma-dependent mechanism. The Journal of biological chemistry 18 20435886
2007 Stargazin interaction with alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors is critically dependent on the amino acid at the narrow constriction of the ion channel. The Journal of biological chemistry 18 17483093
2021 Caspase-1/IL-1β represses membrane transport of GluA1 by inhibiting the interaction between Stargazin and GluA1 in Alzheimer's disease. Molecular medicine (Cambridge, Mass.) 17 33509083
2019 CACNG2 polymorphisms associate with chronic pain after mastectomy. Pain 17 30371558
2018 Stargazin Dephosphorylation Mediates Homeostatic Synaptic Downscaling of Excitatory Synapses. Frontiers in molecular neuroscience 16 30271322
2008 Genetic absence epilepsy rats from Strasbourg have increased corticothalamic expression of stargazin. Neurobiology of disease 16 18556211
2006 Stargazin mutation impairs cerebellar synaptogenesis, synaptic maturation and synaptic protein distribution. Brain research 16 17070505
2022 Aberrant hippocampal transmission and behavior in mice with a stargazin mutation linked to intellectual disability. Molecular psychiatry 15 35256745
2012 From mouse to humans: discovery of the CACNG2 pain susceptibility gene. Clinical genetics 15 22775325
2012 Autoinactivation of the stargazin-AMPA receptor complex: subunit-dependency and independence from physical dissociation. PloS one 14 23166629
2019 Study of 45 candidate genes suggests CACNG2 may be associated with lithium response in bipolar disorder. Journal of affective disorders 12 30738251
2011 Calpain-mediated regulation of stargazin in adult rat brain. Neuroscience 12 21256931
2020 miR-339 Promotes Hypoxia-Induced Neuronal Apoptosis and Impairs Cell Viability by Targeting FGF9/CACNG2 and Mediating MAPK Pathway in Ischemic Stroke. Frontiers in neurology 11 32587563
2012 Evidence for association of bipolar disorder to haplotypes in the 22q12.3 region near the genes stargazin, IFT27 and parvalbumin. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 10 23038240
2000 Genetic localization of the Ca2+ channel gene CACNG2 near SCA10 on chromosome 22q13. Epilepsia 10 10643919
2022 Exosomal circ-CACNG2 promotes cardiomyocyte apoptosis in multiple myeloma via modulating miR-197-3p/caspase3 axis. Experimental cell research 9 35649477
2006 Additive regulation of GluR1 by stargazin and serum- and glucocorticoid-inducible kinase isoform SGK3. Pflugers Archiv : European journal of physiology 9 16485113
2011 c-Fos, Arc, and stargazin expression in rat eyeblink conditioning. Behavioral neuroscience 8 21319893
2011 Stargazin-related protein γ₇ is associated with signalling endosomes in superior cervical ganglion neurons and modulates neurite outgrowth. Journal of cell science 8 21610096
2011 Two modes of interaction between the membrane-embedded TARP stargazin's C-terminal domain and the bilayer visualized by electron crystallography. Journal of structural biology 7 21426941
2018 Regulatory Architecture of the Neuronal Cacng2/Tarpγ2 Gene Promoter: Multiple Repressive Domains, a Polymorphic Regulatory Short Tandem Repeat, and Bidirectional Organization with Co-regulated lncRNAs. Journal of molecular neuroscience : MN 6 30478755
2016 Learning to cope with stress modulates anterior cingulate cortex stargazin expression in monkeys and mice. Neurobiology of learning and memory 6 27003116
2019 Stargazin and γ4 slow the channel opening and closing rates of GluA4 AMPA receptors. Scientific reports 5 31267004
2015 Zebrafish TARP Cacng2 is required for the expression and normal development of AMPA receptors at excitatory synapses. Developmental neurobiology 5 26178704
2022 Association between CACNG2 polymorphisms (rs4820242, rs2284015 and rs2284017) and chronic peripheral neuropathic pain risk in a Mexican population. European review for medical and pharmacological sciences 3 35776036
2018 Stargazin differentially modulates ampakine gating kinetics and pharmacology. Biochemical pharmacology 3 29330065
2025 Exploring the impact of the stargazin V143L mutation on the dynamics of the AMPA receptor: stargazin complex. Frontiers in cellular neuroscience 2 39895898
2010 Further characterization of regulation of Ca(V)2.2 by stargazin. Channels (Austin, Tex.) 2 21139418
2023 Molecular cloning of the gene promoter encoding the human CaVγ2/Stargazin divergent transcript (CACNG2-DT): characterization and regulation by the cAMP-PKA/CREB signaling pathway. Frontiers in physiology 1 38033343

Missed literature

Know a paper Affinage missed for CACNG2? Flag it for the maintainers and the community.

No submissions yet.