Functional properties of a new voltage-dependent calcium channel auxiliary subunit gene (CACNA2D2)

Boning Gao, Yoshitaka Sekido, Anton Maximov, Mohamad Saad, Eva Forgacs, Farida Latif, Ming H. Wei, Michael Lerman, Jung Ha Lee, Edward Perez-Reyes, Ilya Bezprozvanny, John D. Minna

Research output: Contribution to journalArticle

142 Scopus citations

Abstract

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 α(1B) and β3 subunits in Xenopus oocytes, α2δ-2 increased peak size of the N-type Ca2+ currents 9-fold, and when co- expressed with α(1C) or α(1G) 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.

Original languageEnglish (US)
Pages (from-to)12237-12242
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number16
DOIs
StatePublished - Apr 21 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Gao, B., Sekido, Y., Maximov, A., Saad, M., Forgacs, E., Latif, F., Wei, M. H., Lerman, M., Lee, J. H., Perez-Reyes, E., Bezprozvanny, I., & Minna, J. D. (2000). Functional properties of a new voltage-dependent calcium channel auxiliary subunit gene (CACNA2D2). Journal of Biological Chemistry, 275(16), 12237-12242. https://doi.org/10.1074/jbc.275.16.12237