CACNG2 explained

Calcium channel, voltage-dependent, gamma subunit 2, also known as CACNG2 or stargazin is a protein that in humans is encoded by the CACNG2 gene.^[1]

Function

L-type calcium channels are composed of five subunits. The protein encoded by this gene represents one of these subunits, gamma, and is one of several gamma subunit proteins. It is an integral membrane protein that is thought to stabilize the calcium channel in an inactive (closed) state. This protein is similar to the mouse stargazin protein, mutations in which having been associated with absence seizures, also known as petit-mal or spike-wave seizures. This gene is a member of the neuronal calcium channel gamma subunit gene subfamily of the PMP-22/EMP/MP20 family.^[1]

Stargazin is involved in the transportation of AMPA receptors to the synaptic membrane, and the regulation of their receptor rate constants — via its extracellular domain — once it is there. As it is highly expressed throughout the cerebral cortex, it is likely to have an important role in learning within these areas, due to the importance of AMPA receptors in LTP.

Clinical significance

Disruptions of CACNG2 have been implicated in autism.^[2]

Interactions

CACNG2 has been shown to interact with GRIA4,^[3] DLG4,^{[3] [4]} and MAGI2.^[5]

See also

• Voltage-dependent calcium channel

Further reading

• Powers PA, Liu S, Hogan K, Gregg RG . Molecular characterization of the gene encoding the gamma subunit of the human skeletal muscle 1,4-dihydropyridine-sensitive Ca2+ channel (CACNLG), cDNA sequence, gene structure, and chromosomal location . The Journal of Biological Chemistry . 268 . 13 . 9275–9279 . May 1993 . 8387489 . 10.1016/S0021-9258(18)98346-8 . free .
• Black JL, Lennon VA . Identification and cloning of putative human neuronal voltage-gated calcium channel gamma-2 and gamma-3 subunits: neurologic implications . Mayo Clinic Proceedings . 74 . 4 . 357–361 . April 1999 . 10221464 . 10.4065/74.4.357 .
• Burgess DL, Matsuura T, Ashizawa T, Noebels JL . Genetic localization of the Ca2+ channel gene CACNG2 near SCA10 on chromosome 22q13 . Epilepsia . 41 . 1 . 24–27 . January 2000 . 10643919 . 10.1111/j.1528-1157.2000.tb01500.x . free .
• Chen L, Chetkovich DM, Petralia RS, Sweeney NT, Kawasaki Y, Wenthold RJ, Bredt DS, Nicoll RA . Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms . Nature . 408 . 6815 . 936–943 . 2001 . 11140673 . 10.1038/35050030 . 4427689 . 2000Natur.408..936C .
• Burgess DL, Gefrides LA, Foreman PJ, Noebels JL . A cluster of three novel Ca2+ channel gamma subunit genes on chromosome 19q13.4: evolution and expression profile of the gamma subunit gene family . Genomics . 71 . 3 . 339–350 . February 2001 . 11170751 . 10.1006/geno.2000.6440 .
• Choi J, Ko J, Park E, Lee JR, Yoon J, Lim S, Kim E . Phosphorylation of stargazin by protein kinase A regulates its interaction with PSD-95 . The Journal of Biological Chemistry . 277 . 14 . 12359–12363 . April 2002 . 11805122 . 10.1074/jbc.M200528200 . free .
• Schnell E, Sizemore M, Karimzadegan S, Chen L, Bredt DS, Nicoll RA . 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 . 99 . 21 . 13902–13907 . October 2002 . 12359873 . 129795 . 10.1073/pnas.172511199 . free . 2002PNAS...9913902S .
• Moss FJ, Dolphin AC, Clare JJ . 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 . 4 . 23 . September 2003 . 14505496 . 270087 . 10.1186/1471-2202-4-23 . free .
• Tomita S, Fukata M, Nicoll RA, Bredt DS . Dynamic interaction of stargazin-like TARPs with cycling AMPA receptors at synapses . Science . 303 . 5663 . 1508–1511 . March 2004 . 15001777 . 10.1126/science.1090262 . 46012559 . 2004Sci...303.1508T .
• Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I . A genome annotation-driven approach to cloning the human ORFeome . Genome Biology . 5 . 10 . R84 . 2005 . 15461802 . 545604 . 10.1186/gb-2004-5-10-r84 . free .
• Yamazaki M, Ohno-Shosaku T, Fukaya M, Kano M, Watanabe M, Sakimura K . A novel action of stargazin as an enhancer of AMPA receptor activity . Neuroscience Research . 50 . 4 . 369–374 . December 2004 . 15567474 . 10.1016/j.neures.2004.10.002 . 407088 .
• 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 . The Journal of Neuroscience . 25 . 10 . 2682–2686 . March 2005 . 15758178 . 6725153 . 10.1523/JNEUROSCI.4834-04.2005 . free .
• Stiffler MA, Grantcharova VP, Sevecka M, MacBeath G . Uncovering quantitative protein interaction networks for mouse PDZ domains using protein microarrays . Journal of the American Chemical Society . 128 . 17 . 5913–5922 . May 2006 . 16637659 . 2533859 . 10.1021/ja060943h .
• Bedoukian MA, Weeks AM, Partin KM . Different domains of the AMPA receptor direct stargazin-mediated trafficking and stargazin-mediated modulation of kinetics . The Journal of Biological Chemistry . 281 . 33 . 23908–23921 . August 2006 . 16793768 . 10.1074/jbc.M600679200 . free .
• Körber C, Werner M, Hoffmann J, Sager C, Tietze M, Schmid SM, Kott S, Hollmann M . 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 . 282 . 26 . 18758–18766 . June 2007 . 17483093 . 10.1074/jbc.M611182200 . free .

Notes and References

1. Web site: Entrez Gene: CACNG2 calcium channel, voltage-dependent, gamma subunit 2.
2. Brandler WM, Antaki D, Gujral M, Noor A, Rosanio G, Chapman TR, Barrera DJ, Lin GN, Malhotra D, Watts AC, Wong LC, Estabillo JA, Gadomski TE, Hong O, Fajardo KV, Bhandari A, Owen R, Baughn M, Yuan J, Solomon T, Moyzis AG, Maile MS, Sanders SJ, Reiner GE, Vaux KK, Strom CM, Zhang K, Muotri AR, Akshoomoff N, Leal SM, Pierce K, Courchesne E, Iakoucheva LM, Corsello C, Sebat J . Frequency and Complexity of De Novo Structural Mutation in Autism . American Journal of Human Genetics . 98 . 4 . 667–679 . April 2016 . 27018473 . 4833290 . 10.1016/j.ajhg.2016.02.018 .
3. Chen L, Chetkovich DM, Petralia RS, Sweeney NT, Kawasaki Y, Wenthold RJ, Bredt DS, Nicoll RA . Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms . Nature . 408 . 6815 . 936–943 . 2000 . 11140673 . 10.1038/35050030 . 4427689 . 2000Natur.408..936C .
4. Choi J, Ko J, Park E, Lee JR, Yoon J, Lim S, Kim E . Phosphorylation of stargazin by protein kinase A regulates its interaction with PSD-95 . The Journal of Biological Chemistry . 277 . 14 . 12359–12363 . April 2002 . 11805122 . 10.1074/jbc.M200528200 . free .
5. Deng F, Price MG, Davis CF, Mori M, Burgess DL . Stargazin and other transmembrane AMPA receptor regulating proteins interact with synaptic scaffolding protein MAGI-2 in brain . The Journal of Neuroscience . 26 . 30 . 7875–7884 . July 2006 . 16870733 . 6674230 . 10.1523/JNEUROSCI.1851-06.2006 . free .