Functional Properties of a New Voltage-dependent Calcium Channel α2δ Auxiliary Subunit Gene (CACNA2D2) *
By B. Gao, Y. Sekido, A. Maximov, M. Saad, É. Forgács, F. Latif, M. Wei, M. Lerman, Jung-Ha Lee, E. Perez-Reyes and 2 more. Journal of Biological Chemistry, 2000
178 citations recorded by the source corpus.
We have positionally cloned and characterized a new calcium channel auxiliary subunit, α2δ-2 (CACNA2D2), which shares 56% amino acid identity with the known α2δ-1 subunit. The gene maps to the critical human tumor suppressor gene region in chromosome 3p21.3, showing very frequent allele loss and occasional homozygous deletions in lung, breast, and other cancers. The tissue distribution of α2δ-2 expression is different from α2δ-1, and α2δ-2 mRNA is most abundantly expressed in lung and testis and well expressed in brain, heart, and pancreas. In contrast, α2δ-1 is expressed predominantly in brain, heart, and skeletal muscle. When co-expressed (via cRNA injections) with α1B and β3subunits in Xenopus oocytes, α2δ-2 increased peak size of the N-type Ca2+ currents 9-fold, and when co-expressed with α1C or α1G subunits in Xenopus oocytes increased peak size of L-type channels 2-fold and T-type channels 1.8-fold, respectively. Anti-peptide antibodies detect the expression of a 129-kDa α2δ-2 polypeptide in some but not all lung tumor cells. We conclude that the α2δ-2 gene encodes a functional auxiliary subunit of voltage-gated Ca2+ channels. Because of its chromosomal location and expression patterns, CACNA2D2 needs to be explored as a potential tumor suppressor gene linking Ca2+signaling and lung, breast, and other cancer pathogenesis. The homologous location on mouse chromosome 9 is also the site of the mouse neurologic mutant ducky (du), and thus,CACNA2D2 is also a candidate gene for this inherited idiopathic generalized epilepsy syndrome.
Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/36f3a1aa1dbee56f5d789611e00e21a6a97bc652
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Citations in the corpus
- Differential distribution of voltage‐gated calcium channel alpha‐2 delta (α2δ) subunit mRNA‐containing cells in the rat central nervous system and the dorsal root ganglia (2005, methodology): “…in the brain and, like 2 -2, the 2 -3 subunit is involved in the enhancement and modulation of the currents through several different high-voltage-activated (HVA) and low-voltage-activated (LVA) Ca channels (Klugbauer et al., 1999; Gao et al., 2000; Hobom et al., 2000; Marais et al., 2001).”
- Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. (2001, methodology): “Western blot analysis was performed as described previously ( 30 ) to verify protein expression of the transfected genes.”