Cav2.1
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The Cav2.1 P/Q voltage-dependent calcium channel is encoded by the CACNA1A gene.
Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas, the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1A subunit, which is predominantly expressed in neuronal tissue. Mutations in this gene are associated with 2 neurologic disorders, familial hemiplegic migraine and episodic ataxia 2. This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants have been described, however, the full-length nature of not all is known. In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. But in another set of variants, an insertion extends the coding region to include the (CAG)n-repeats which encode a polyglutamine tract. Expansion of the (CAG)n-repeats from the normal 4-16 to 21-28 in the coding region is associated with spinocerebellar ataxia 6.[1]
Interactions
Cav2.1 has been shown to interact with CACNB4.[2][3]
References
- ↑ "Entrez Gene: CACNA1A calcium channel, voltage-dependent, P/Q type, alpha 1A subunit".
- ↑ Walker, D; Bichet D, Campbell K P, De Waard M (Jan 1998). "A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel alpha 1A subunit". J. Biol. Chem. (UNITED STATES) 273 (4): 2361–2367. doi:10.1074/jbc.273.4.2361. ISSN 0021-9258. PMID 9442082.
- ↑ Walker, D; Bichet D, Geib S, Mori E, Cornet V, Snutch T P, Mori Y, De Waard M (Apr 1999). "A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca2+ channel activation". J. Biol. Chem. (UNITED STATES) 274 (18): 12383–12390. doi:10.1074/jbc.274.18.12383. ISSN 0021-9258. PMID 10212211.
Further reading
- Terwindt G, Kors E, Haan J et al. (2002). "Mutation analysis of the CACNA1A calcium channel subunit gene in 27 patients with sporadic hemiplegic migraine". Arch. Neurol. 59 (6): 1016–1018. doi:10.1001/archneur.59.6.1016. PMID 12056940.
- Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (2006). "International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels". Pharmacol. Rev. 57 (4): 411–425. doi:10.1124/pr.57.4.5. PMID 16382099.
- Perez-Reyes E, Castellano A, Kim HS et al. (1992). "Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel". J. Biol. Chem. 267 (3): 1792–7. PMID 1370480.
- Barry EL, Viglione MP, Kim YI, Froehner SC (1995). "Expression and antibody inhibition of P-type calcium channels in human small-cell lung carcinoma cells". J. Neurosci. 15 (1 Pt 1): 274–83. PMID 7823133.
- Joutel A, Bousser MG, Biousse V et al. (1993). "A gene for familial hemiplegic migraine maps to chromosome 19". Nat. Genet. 5 (1): 40–45. doi:10.1038/ng0993-40. PMID 8220421.
- Margolis RL, Breschel TS, Li SH et al. (1996). "Characterization of cDNA clones containing CCA trinucleotide repeats derived from human brain". Somat. Cell Mol. Genet. 21 (4): 279–284. doi:10.1007/BF02255782. PMID 8525433.
- Rettig J, Sheng ZH, Kim DK et al. (1996). "Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25". Proc. Natl. Acad. Sci. U.S.A. 93 (14): 7363–7368. doi:10.1073/pnas.93.14.7363. PMC 38990. PMID 8692999.
- Diriong S, Lory P, Williams ME et al. (1997). "Chromosomal localization of the human genes for alpha 1A, alpha 1B, and alpha 1E voltage-dependent Ca2+ channel subunits". Genomics 30 (3): 605–609. doi:10.1006/geno.1995.1284. PMID 8825650.
- Ophoff RA, Terwindt GM, Vergouwe MN et al. (1996). "Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4". Cell 87 (3): 543–552. doi:10.1016/S0092-8674(00)81373-2. PMID 8898206.
- Zhuchenko O, Bailey J, Bonnen P et al. (1997). "Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel". Nat. Genet. 15 (1): 62–69. doi:10.1038/ng0197-62. PMID 8988170.
- De Waard M, Liu H, Walker D et al. (1997). "Direct binding of G-protein betagamma complex to voltage-dependent calcium channels". Nature 385 (6615): 446–450. doi:10.1038/385446a0. PMID 9009193.
- Qin N, Platano D, Olcese R et al. (1997). "Direct interaction of gbetagamma with a C-terminal gbetagamma-binding domain of the Ca2+ channel alpha1 subunit is responsible for channel inhibition by G protein-coupled receptors". Proc. Natl. Acad. Sci. U.S.A. 94 (16): 8866–8871. doi:10.1073/pnas.94.16.8866. PMC 23172. PMID 9238069.
- Riess O, Schöls L, Bottger H et al. (1997). "SCA6 is caused by moderate CAG expansion in the alpha1A-voltage-dependent calcium channel gene". Hum. Mol. Genet. 6 (8): 1289–1293. doi:10.1093/hmg/6.8.1289. PMID 9259275.
- Jodice C, Mantuano E, Veneziano L et al. (1998). "Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p". Hum. Mol. Genet. 6 (11): 1973–1978. doi:10.1093/hmg/6.11.1973. PMID 9302278.
- Charvin N, L'evêque C, Walker D et al. (1997). "Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alpha1A subunit of the P/Q-type calcium channel". EMBO J. 16 (15): 4591–4596. doi:10.1093/emboj/16.15.4591. PMC 1170085. PMID 9303303.
- Ishikawa K, Tanaka H, Saito M et al. (1997). "Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1". Am. J. Hum. Genet. 61 (2): 336–346. doi:10.1086/514867. PMC 1715894. PMID 9311738.
- Walker D, Bichet D, Campbell KP, De Waard M (1998). "A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel alpha 1A subunit". J. Biol. Chem. 273 (4): 2361–2367. doi:10.1074/jbc.273.4.2361. PMID 9442082.
- Yue Q, Jen JC, Thwe MM et al. (1998). "De novo mutation in CACNA1A caused acetazolamide-responsive episodic ataxia". Am. J. Med. Genet. 77 (4): 298–301. doi:10.1002/(SICI)1096-8628(19980526)77:4<298::AID-AJMG9>3.0.CO;2-J. PMID 9600739.
- Hans M, Urrutia A, Deal C et al. (1999). "Structural elements in domain IV that influence biophysical and pharmacological properties of human alpha1A-containing high-voltage-activated calcium channels". Biophys. J. 76 (3): 1384–1400. doi:10.1016/S0006-3495(99)77300-5. PMC 1300117. PMID 10049321.
- Walker D, Bichet D, Geib S et al. (1999). "A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca2+ channel activation". J. Biol. Chem. 274 (18): 12383–12390. doi:10.1074/jbc.274.18.12383. PMID 10212211.
External links
- GeneReviews/NCBI/NIH/UW entry on Familial Hemiplegic Migraine
- GeneReviews/NCBI/NIH/UW entry on Episodic ataxia type 2
- GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia Type 6
- CACNA1A protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
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