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 γ subunit family, with a novel gene structure and striking properties. Unlike the genes of other potential γ 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 γ(7). Expression of human γ(7) has been localized specifically to brain. N-type current through Ca(V)2.2 channels was almost abolished when co-expressed transiently with γ(7) in either Xenopus oocytes or COS-7 cells. Furthermore, immunocytochemistry and western blots show that γ(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 γ(7) was observed on pre-existing endogenous N-type calcium channels in sympathetic neurones. Low homology to the stargazin-like γ subunits, different gene structure and the unique functional properties of γ(7) imply that it represents a distinct subdivision of the family of proteins identified by their structural and sequence homology to stargazin.