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  • The EMBO Journal (2002) 21, 1514 - 1523
  • doi:10.1093/emboj/21.7.1514

The novel product of a five-exon stargazin-related gene abolishes CaV2.2 calcium channel expression

Fraser J. Moss1, Patricia Viard1,4, Anthony Davies1,4, Federica Bertaso1, Karen M. Page1, Alex Graham1, Carles Cantí1, Mary Plumpton2, Christopher Plumpton3, Jeffrey J. Clare3 and Annette C. Dolphin1

  1. Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
  2. Bioinformatics Unit, GlaxoSmithKline, Medicines Research Center, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK
  3. Gene Expression and Protein Biochemistry, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK
  4. P.Viard, A.Davies and F.Bertaso contributed equally to this work

Correspondence to:

Annette C. Dolphin, E-mail: a.dolphin@ucl.ac.uk

Received 14 December 2001; Accepted 7 February 2002; Revised 5 February 2002

We have cloned and characterized a new member of the voltage-dependent Ca2+ channel gamma subunit family, with a novel gene structure and striking properties. Unlike the genes of other potential gamma subunits identified by their homology to the stargazin gene, CACNG7 is a five-, and not four-exon gene whose mRNA encodes a protein we have designated gamma7. Expression of human gamma7 has been localized specifically to brain. N-type current through CaV2.2 channels was almost abolished when co-expressed transiently with gamma7 in either Xenopus oocytes or COS-7 cells. Furthermore, immunocytochemistry and western blots show that gamma7 has this effect by causing a large reduction in expression of CaV2.2 rather than by interfering with trafficking or biophysical properties of the channel. No effect of transiently expressed gamma7 was observed on pre-existing endogenous N-type calcium channels in sympathetic neurones. Low homology to the stargazin-like gamma subunits, different gene structure and the unique functional properties of gamma7 imply that it represents a distinct subdivision of the family of proteins identified by their structural and sequence homology to stargazin.

  • Keywords:

    • calcium channel,
    • expression,
    • gamma subunit,
    • stargazin,
    • suppression