The novel product of a five-exon stargazin-related gene abolishes Ca(V)2.2 calcium channel expression.
We have cloned and characterized a new member of the voltage-dependent Ca(2+) 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 gamma(7). Expression of human gamma(7) has been localized specifically to brain. N-type current through Ca(V)2.2 channels was almost abolished when co-expressed transiently with gamma(7) in either Xenopus oocytes or COS-7 cells. Furthermore, immunocytochemistry and western blots show that gamma(7) has this effect by causing a large reduction in expression of Ca(V)2.2 rather than by interfering with trafficking or biophysical properties of the channel. No effect of transiently expressed gamma(7) 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 gamma(7) imply that it represents a distinct subdivision of the family of proteins identified by their structural and sequence homology to stargazin.
Moss
Fraser J
FJ
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Viard
Patricia
P
Davies
Anthony
A
Bertaso
Federica
F
Page
Karen M
KM
Graham
Alex
A
Cantí
Carles
C
Plumpton
Mary
M
Plumpton
Christopher
C
Clare
Jeffrey J
JJ
Dolphin
Annette C
AC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002118:Calcium; D015220:Calcium Channels / Q000235:genetics*; D020864:Calcium Channels, N-Type / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005091:Exons; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation; D006801:Humans; D026901:Membrane Transport Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D051670:Shaw Potassium Channels; D013564:Sympathetic Nervous System / Q000166:cytology; D014018:Tissue Distribution; D014981:Xenopus
C491912:CACNG2 protein, human; C456020:CACNG7 protein, human; C113940:Cacng2 protein, mouse; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D018076:DNA, Complementary; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins; D051670:Shaw Potassium Channels; D002118:Calcium