6kzp

Structural highlights

Disease

[CAC1G_HUMAN] Spinocerebellar ataxia type 42. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

[CAC1G_HUMAN] Voltage-sensitive calcium channels (VSCC) 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, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group and are strongly blocked by mibefradil. A particularity of this type of channel is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.^{[1] [2] [3] [4] [5]}

References

1. ↑ Cribbs LL, Gomora JC, Daud AN, Lee JH, Perez-Reyes E. Molecular cloning and functional expression of Ca(v)3.1c, a T-type calcium channel from human brain. FEBS Lett. 2000 Jan 21;466(1):54-8. doi: 10.1016/s0014-5793(99)01756-1. PMID:10648811 doi:http://dx.doi.org/10.1016/s0014-5793(99)01756-1
2. ↑ Monteil A, Chemin J, Bourinet E, Mennessier G, Lory P, Nargeot J. Molecular and functional properties of the human alpha(1G) subunit that forms T-type calcium channels. J Biol Chem. 2000 Mar 3;275(9):6090-100. PMID:10692398
3. ↑ Coutelier M, Blesneac I, Monteil A, Monin ML, Ando K, Mundwiller E, Brusco A, Le Ber I, Anheim M, Castrioto A, Duyckaerts C, Brice A, Durr A, Lory P, Stevanin G. A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia. Am J Hum Genet. 2015 Nov 5;97(5):726-37. doi: 10.1016/j.ajhg.2015.09.007. Epub, 2015 Oct 8. PMID:26456284 doi:http://dx.doi.org/10.1016/j.ajhg.2015.09.007
4. ↑ Morino H, Matsuda Y, Muguruma K, Miyamoto R, Ohsawa R, Ohtake T, Otobe R, Watanabe M, Maruyama H, Hashimoto K, Kawakami H. A mutation in the low voltage-gated calcium channel CACNA1G alters the physiological properties of the channel, causing spinocerebellar ataxia. Mol Brain. 2015 Dec 29;8:89. doi: 10.1186/s13041-015-0180-4. PMID:26715324 doi:http://dx.doi.org/10.1186/s13041-015-0180-4
5. ↑ Chemin J, Siquier-Pernet K, Nicouleau M, Barcia G, Ahmad A, Medina-Cano D, Hanein S, Altin N, Hubert L, Bole-Feysot C, Fourage C, Nitschke P, Thevenon J, Rio M, Blanc P, Vidal C, Bahi-Buisson N, Desguerre I, Munnich A, Lyonnet S, Boddaert N, Fassi E, Shinawi M, Zimmerman H, Amiel J, Faivre L, Colleaux L, Lory P, Cantagrel V. De novo mutation screening in childhood-onset cerebellar atrophy identifies gain-of-function mutations in the CACNA1G calcium channel gene. Brain. 2018 Jul 1;141(7):1998-2013. doi: 10.1093/brain/awy145. PMID:29878067 doi:http://dx.doi.org/10.1093/brain/awy145
6. ↑ Zhao Y, Huang G, Wu Q, Wu K, Li R, Lei J, Pan X, Yan N. Cryo-EM structures of apo and antagonist-bound human Cav3.1. Nature. 2019 Nov 25. pii: 10.1038/s41586-019-1801-3. doi:, 10.1038/s41586-019-1801-3. PMID:31766050 doi:http://dx.doi.org/10.1038/s41586-019-1801-3