8.A.16 The Ca Channel Auxiliary Subunit γ1-γ8 (CCAγ) Family
Calcium channel γ1-8 auxiliary subunits all share limited sequence similarity and belong to a single family. They have the same topology of four transmembrane segments (a claudin domain) including a large loop between TMSs 1 and 2, a characteristic of TC family 1.H.2. All neuronal γ-subunits share a C-terminal consensus site for phosphorylation by cAMP/cGMP-dependent protein kinases. They associate with α-subunits of voltage-gated Ca2 channels (TC #1.A.1.11). γ2 (also called stargazin) and γ3 have been shown to associate with P/Q- and N-type channels. Regulation by stargazin may occur via the G-beta-gamma subunits of Ca(v)2.2 (TC# 1.A.1.11.19) and G protein-activated inward rectifier potassium channels, GIRK (see 1.A.2.1.3; Tselnicker and Dascal 2010). γ3 and γ4 are express only in neuronal tissues. γ1 and γ6 have two glycosylation sites, and this may be a characteristic of all γ-subunits. These putative calcium channel auxiliary subunits are found in eukaryotic genomes including human, rat, mouse, fugu fish, chicken, zebra fish, fruitfly, and C. elegans. This family may function in the assembly, modulation of function and/or maintenance of structure of skeletal muscle and brain calcium channels. γ1 controls the dihydropyridine-sensitive L-type skeletal muscle calcium channel (TC #1.A.1.11.2).