Cacng2

Summary

Gene Symbol: Cacng2
Description: calcium voltage-gated channel auxiliary subunit gamma 2
Alias: Ipr328, voltage-dependent calcium channel gamma-2 subunit, TARP gamma-2, calcium channel, voltage-dependent, gamma subunit 2, neuronal voltage-gated calcium channel gamma-2 subunit, stargazin, transmembrane AMPAR regulatory protein gamma-2
Species: rat
Products:     Cacng2

Top Publications

  1. Chu P, Robertson H, Best P. Calcium channel gamma subunits provide insights into the evolution of this gene family. Gene. 2001;280:37-48 pubmed
  2. Zhang Y, Mori M, Burgess D, Noebels J. Mutations in high-voltage-activated calcium channel genes stimulate low-voltage-activated currents in mouse thalamic relay neurons. J Neurosci. 2002;22:6362-71 pubmed
    ..These alterations increase the probability for abnormal thalamocortical synchronization and absence epilepsy in tg, lh, and stg mice. ..
  3. Schnell E, Sizemore M, Karimzadegan S, Chen L, Bredt D, Nicoll R. Direct interactions between PSD-95 and stargazin control synaptic AMPA receptor number. Proc Natl Acad Sci U S A. 2002;99:13902-7 pubmed
    ..two PDZ domains of synaptic PSD-95 (postsynaptic density protein of 95 kDa) to the AMPAR-associated protein, stargazin. Increasing the level of synaptic PSD-95 recruits new AMPARs to synapses without changing the number of surface ..
  4. Shi Y, Suh Y, Milstein A, Isozaki K, Schmid S, Roche K, et al. Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating. Proc Natl Acad Sci U S A. 2010;107:16315-9 pubmed publisher
    ..This neuronal role is more consistent with that of an endoplasmic reticulum (ER) chaperone rather than a bona fide auxiliary subunit. ..
  5. Kim S, Thompson R. c-Fos, Arc, and stargazin expression in rat eyeblink conditioning. Behav Neurosci. 2011;125:117-23 pubmed publisher
    ..A significant increase in Stargazin expression was also identified in the whole cerebellum...
  6. Schwenk J, Harmel N, Zolles G, Bildl W, Kulik A, Heimrich B, et al. Functional proteomics identify cornichon proteins as auxiliary subunits of AMPA receptors. Science. 2009;323:1313-9 pubmed publisher
    ..These results demonstrate that cornichons are intrinsic auxiliary subunits of native AMPARs and provide previously unknown molecular determinants for glutamatergic neurotransmission in the central nervous system. ..
  7. Matsuda S, Miura E, Matsuda K, Kakegawa W, Kohda K, Watanabe M, et al. Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking adaptor protein AP-4. Neuron. 2008;57:730-45 pubmed publisher
    ..These results indicate that AP-4 may regulate proper somatodendritic-specific distribution of its cargo proteins, including AMPA receptor-TARP complexes and the autophagic pathway in neurons. ..
  8. Bats C, Groc L, Choquet D. The interaction between Stargazin and PSD-95 regulates AMPA receptor surface trafficking. Neuron. 2007;53:719-34 pubmed
    Accumulation of AMPA receptors at synapses is a fundamental feature of glutamatergic synaptic transmission. Stargazin, a member of the TARP family, is an AMPAR auxiliary subunit allowing interaction of the receptor with scaffold proteins ..
  9. Joiner M, Lise M, Yuen E, Kam A, Zhang M, Hall D, et al. Assembly of a beta2-adrenergic receptor--GluR1 signalling complex for localized cAMP signalling. EMBO J. 2010;29:482-95 pubmed publisher
    ..signalling complex with the AMPA-type glutamate receptor subunit GluR1, which is linked to the beta(2)AR through stargazin and PSD-95 and their homologues...

More Information

Publications42

  1. Itakura M, Watanabe I, Sugaya T, Takahashi M. Direct association of the unique C-terminal tail of transmembrane AMPA receptor regulatory protein ?-8 with calcineurin. FEBS J. 2014;281:1366-78 pubmed publisher
    ..The classical TARP family consists of four members: stargazin/?-2, ?-3, ?-4 and ?-8...
  2. Milstein A, Zhou W, Karimzadegan S, Bredt D, Nicoll R. TARP subtypes differentially and dose-dependently control synaptic AMPA receptor gating. Neuron. 2007;55:905-18 pubmed
  3. Bedoukian M, Whitesell J, Peterson E, Clay C, Partin K. The stargazin C terminus encodes an intrinsic and transferable membrane sorting signal. J Biol Chem. 2008;283:1597-600 pubmed
    ..of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors is regulated by their auxiliary subunit, stargazin. Association with stargazin enhances alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor surface ..
  4. Selvakumar B, Campbell P, Milovanovic M, Park D, West A, Snyder S, et al. AMPA receptor upregulation in the nucleus accumbens shell of cocaine-sensitized rats depends upon S-nitrosylation of stargazin. Neuropharmacology. 2014;77:28-38 pubmed publisher
    ..Nitric oxide (NO) regulates AMPAR trafficking in the brain by S-nitrosylation of the AMPAR auxiliary subunit, stargazin, leading to increased AMPAR surface expression...
  5. Larsson M, Agalave N, Watanabe M, Svensson C. Distribution of transmembrane AMPA receptor regulatory protein (TARP) isoforms in the rat spinal cord. Neuroscience. 2013;248:180-93 pubmed publisher
    ..transmission, we have mapped the localization of five of the known TARP isoforms, namely ?-2 (also known as stargazin), ?-3, ?-4, ?-7 and ?-8, in the rat spinal cord...
  6. Ferrario C, Loweth J, Milovanovic M, Ford K, Galiñanes G, Heng L, et al. Alterations in AMPA receptor subunits and TARPs in the rat nucleus accumbens related to the formation of Ca²?-permeable AMPA receptors during the incubation of cocaine craving. Neuropharmacology. 2011;61:1141-51 pubmed publisher
    ..Overall, AMPAR plasticity in the incubation model shares some features with better described forms of synaptic plasticity, although the timing of the phenomenon and the persistence of related neuroadaptations are significantly different...
  7. Matsuda S, Kakegawa W, Budisantoso T, Nomura T, Kohda K, Yuzaki M. Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression. Nat Commun. 2013;4:2759 pubmed publisher
    ..Here we show that stargazin, a transmembrane AMPA receptor regulatory protein, forms a ternary complex with adaptor proteins AP-2 and AP-3A ..
  8. Kaja S, Todorov B, van de Ven R, Ferrari M, Frants R, van den Maagdenberg A, et al. Redundancy of Cav2.1 channel accessory subunits in transmitter release at the mouse neuromuscular junction. Brain Res. 2007;1143:92-101 pubmed
    ..1 channel function due to alpha(2)delta-2 absence. We conclude that alpha(2)delta-2, beta(4), and gamma(2) accessory subunits are redundant for the transmitter release-mediating function of presynaptic Ca(v)2.1 channels at the mouse NMJ. ..
  9. Zhao Y, Chen S, Yoshioka C, Baconguis I, Gouaux E. Architecture of fully occupied GluA2 AMPA receptor-TARP complex elucidated by cryo-EM. Nature. 2016;536:108-11 pubmed
  10. Chen S, Zhao Y, Wang Y, Shekhar M, Tajkhorshid E, Gouaux E. Activation and Desensitization Mechanism of AMPA Receptor-TARP Complex by Cryo-EM. Cell. 2017;170:1234-1246.e14 pubmed publisher
    ..Structural and computational analysis suggests the full agonist and modulator complex harbors an ion-permeable channel gate, providing the first view of an activated AMPA receptor. ..
  11. Kato A, Siuda E, Nisenbaum E, Bredt D. AMPA receptor subunit-specific regulation by a distinct family of type II TARPs. Neuron. 2008;59:986-96 pubmed publisher
    ..Previous studies identified five mammalian TARPs, gamma-2 (or stargazin), gamma-3, gamma-4, gamma-7, and gamma-8, that enhance AMPA receptor function...
  12. Yu L, Rostamiani K, Hsu Y, Wang Y, Bi X, Baudry M. Calpain-mediated regulation of stargazin in adult rat brain. Neuroscience. 2011;178:13-20 pubmed publisher
    ..b>Stargazin is a member of the family of transmembrane AMPA receptor associated proteins (TARPs), which participates in ..
  13. Priel A, Kolleker A, Ayalon G, Gillor M, Osten P, Stern Bach Y. Stargazin reduces desensitization and slows deactivation of the AMPA-type glutamate receptors. J Neurosci. 2005;25:2682-6 pubmed
    ..b>Stargazin (also termed gamma2) is a member of a recently identified protein family termed transmembrane AMPA receptor ..
  14. Aizawa M, Ito Y, Fukuda H. Pharmacological profiles of generalized absence seizures in lethargic, stargazer and gamma-hydroxybutyrate-treated model mice. Neurosci Res. 1997;29:17-25 pubmed
    ..These results suggest that GABAB receptors play a significant role in the pathogenesis of generalized absence seizures in these models, although the mechanism involved in stargazer mice differ from that in the other two. ..
  15. Tomita S, Chen L, Kawasaki Y, Petralia R, Wenthold R, Nicoll R, et al. Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins. J Cell Biol. 2003;161:805-16 pubmed
    ..alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in cerebellar granule cells requires stargazin, a member of a large family of four-pass transmembrane proteins...
  16. Tomita S, Stein V, Stocker T, Nicoll R, Bredt D. Bidirectional synaptic plasticity regulated by phosphorylation of stargazin-like TARPs. Neuron. 2005;45:269-77 pubmed
    ..Here, we show that the AMPA receptor-associated protein stargazin is quantitatively phosphorylated and that stargazin phosphorylation promotes synaptic trafficking of AMPA ..
  17. Letts V, Mahaffey C, Beyer B, Frankel W. A targeted mutation in Cacng4 exacerbates spike-wave seizures in stargazer (Cacng2) mice. Proc Natl Acad Sci U S A. 2005;102:2123-8 pubmed
    The voltage-dependent calcium channel gamma4 subunit protein, CACNG4, is closely related to the gamma2 subunit, CACNG2. Both are expressed primarily in the brain and share 53% amino acid identity...
  18. Di Pasquale E, Keegan K, Noebels J. Increased excitability and inward rectification in layer V cortical pyramidal neurons in the epileptic mutant mouse Stargazer. J Neurophysiol. 1997;77:621-31 pubmed
    ..This defect could lower the threshold for aberrant thalamocortical spike wave oscillations in vivo, and may contribute to the mechanism of one form of inherited absence epilepsy...
  19. Martínez Turrillas R, Del Rio J, Frechilla D. Neuronal proteins involved in synaptic targeting of AMPA receptors in rat hippocampus by antidepressant drugs. Biochem Biophys Res Commun. 2007;353:750-5 pubmed
    ..Both antidepressants increased the interaction of GluR1 subunit with stargazin and of GluR2/3 with NSF...
  20. Kennard J, Barmanray R, Sampurno S, Ozturk E, Reid C, Paradiso L, et al. Stargazin and AMPA receptor membrane expression is increased in the somatosensory cortex of Genetic Absence Epilepsy Rats from Strasbourg. Neurobiol Dis. 2011;42:48-54 pubmed publisher
    ..We have previously shown that expression of the Transmembrane AMPA receptor Regulatory Protein (TARP), stargazin, is elevated in the somatosensory cortex of GAERS...
  21. Turetsky D, Garringer E, Patneau D. Stargazin modulates native AMPA receptor functional properties by two distinct mechanisms. J Neurosci. 2005;25:7438-48 pubmed
    ..The transmembrane AMPA receptor regulatory protein (TARP) stargazin (gamma2) serves multiple roles in trafficking and stabilizing synaptic AMPA receptors and may be incorporated as ..
  22. Lisman J, Yasuda R, Raghavachari S. Mechanisms of CaMKII action in long-term potentiation. Nat Rev Neurosci. 2012;13:169-82 pubmed publisher
    ..These processes are all localized to stimulated spines and account for the synapse-specificity of LTP. In the later stages of LTP, CaMKII has a structural role in enlarging and strengthening the synapse. ..
  23. Selvakumar B, Huganir R, Snyder S. S-nitrosylation of stargazin regulates surface expression of AMPA-glutamate neurotransmitter receptors. Proc Natl Acad Sci U S A. 2009;106:16440-5 pubmed publisher
    Synaptic plasticity is mediated by changes in the surface expression of AMPA receptors (AMPARs). Stargazin and related transmembrane AMPAR regulatory proteins have emerged as the principal regulators of AMPAR surface expression...
  24. Tomita S, Fukata M, Nicoll R, Bredt D. Dynamic interaction of stargazin-like TARPs with cycling AMPA receptors at synapses. Science. 2004;303:1508-11 pubmed
    ..Synaptic trafficking of AMPA receptors is controlled by stargazin and homologous transmembrane AMPA receptor regulatory proteins (TARPs)...
  25. Hamdan F, Gauthier J, Araki Y, Lin D, Yoshizawa Y, Higashi K, et al. Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet. 2011;88:306-16 pubmed publisher
    ..De novo missense mutations were found in KIF1A, GRIN1, CACNG2, and EPB41L1...
  26. Soto D, Coombs I, Renzi M, Zonouzi M, Farrant M, Cull Candy S. Selective regulation of long-form calcium-permeable AMPA receptors by an atypical TARP, gamma-5. Nat Neurosci. 2009;12:277-85 pubmed publisher
    ..receptors (AMPARs) depend critically on associated transmembrane AMPAR regulatory proteins (TARPs) such as stargazin (gamma-2), no TARP has been described that can specifically regulate the important class of calcium-permeable (..
  27. Inamura M, Itakura M, Okamoto H, Hoka S, Mizoguchi A, Fukazawa Y, et al. Differential localization and regulation of stargazin-like protein, gamma-8 and stargazin in the plasma membrane of hippocampal and cortical neurons. Neurosci Res. 2006;55:45-53 pubmed
    Transmembrane AMPA receptor regulatory proteins (TARPs), including stargazin/gamma-2, are associated with AMPA receptors and participate in their surface delivery and anchoring at the postsynaptic membrane...
  28. Strutz Seebohm N, Seebohm G, Korniychuk G, Baltaev R, Ureche O, Striegel M, et al. Additive regulation of GluR1 by stargazin and serum- and glucocorticoid-inducible kinase isoform SGK3. Pflugers Arch. 2006;452:276-82 pubmed
    The serum- and glucocorticoid-inducible kinase isoform 3 (SGK3) and stargazin have both been shown to enhance the synaptic expression level of GluR1...
  29. Powell K, Kyi M, Reid C, Paradiso L, D Abaco G, Kaye A, et al. Genetic absence epilepsy rats from Strasbourg have increased corticothalamic expression of stargazin. Neurobiol Dis. 2008;31:261-5 pubmed publisher
    b>Stargazin is membrane bound protein involved in trafficking, synapse anchoring and biophysical modulation of AMPA receptors...
  30. Rademacher N, Schmerl B, Lardong J, Wahl M, Shoichet S. MPP2 is a postsynaptic MAGUK scaffold protein that links SynCAM1 cell adhesion molecules to core components of the postsynaptic density. Sci Rep. 2016;6:35283 pubmed publisher
    ..Our results highlight a previously unexplored role for MPP2 at postsynaptic sites as a scaffold that links SynCAM1 cell adhesion molecules to core proteins of the postsynaptic density. ..
  31. Kang M, Guo Y, Huganir R. AMPA receptor and GEF-H1/Lfc complex regulates dendritic spine development through RhoA signaling cascade. Proc Natl Acad Sci U S A. 2009;106:3549-54 pubmed publisher
    ..Altogether, these results strongly suggest that GEF-H1 is an important mediator of AMPA-R activity-dependent structural plasticity in neurons. ..
  32. Ives J, Fung S, Tiwari P, Payne H, Thompson C. Microtubule-associated protein light chain 2 is a stargazin-AMPA receptor complex-interacting protein in vivo. J Biol Chem. 2004;279:31002-9 pubmed
    The ataxic mutant mouse stargazer is a null mutant for stargazin, a protein involved in the regulation of cell surface trafficking and synaptic targeting of AMPA receptors...
  33. Cannady R, Fisher K, Graham C, Crayle J, Besheer J, Hodge C. Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner. Addict Biol. 2017;22:652-664 pubmed publisher
    ..Enhanced activity of plasticity-linked AMPAR-CaMKII signaling in the amygdala may promote escalated alcohol use via increased positive reinforcement during the initial stages of addiction. ..