Logged in as a Visitor.
calcium channel, voltage-dependent, gamma subunit 1
Voltage-dependent calcium channels are composed of five subunits. The protein encoded by CACNG1 (also known as CACNLG) represents one of these subunits, gamma, and is one of two known gamma subunit proteins. This particular gamma subunit is part of skeletal muscle 1,4-dihydropyridine-sensitive calcium channels and is an integral membrane protein that plays a role in excitation-contraction coupling. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family and is located in a cluster with two family members that function as transmembrane AMPA receptor regulatory proteins (TARPs).
The founding member of the gamma subunit family, c1 (cacng1), was first isolated as a subunit of the high-voltage activated (HVA) calcium channel in skeletal muscle (Jay ).
Phylogenetic analysis suggests that all c subunits evolved from a single ancestral gene through tandem repeat and chromosome duplication (Burgess , Chu ). Based on sequence homology and chromosomal linkage the c subunits can be divided into three clusters: (c1, c6), (c5, c7), and (c2, c3, c4, c8) (Burgess , Chu ).
Cacng1 : calcium channel, voltage-dependent, gamma subunit 1
VDCCs are heteromeric proteins composed of a pore-forming a1 subunit and, potentially, as many as three auxiliary subunits: a2d, b, and c (=gamma) (Ertel ).
The eight calcium channel gamma subunits share a predicted structure that includes four transmembrane domains with intracellular N- and C- termini (Fig. 1 in Chen ). They are members of a large protein superfamily (pfam00822, a subset of the tetraspanin supergroup) that also includes claudins, proteins that are important components of tight junctions in epithelia. The c subunits share with the claudins a conserved GLW motif of unknown significance in the first extracellular loop. (Chen )
The c1 and c6 subunits are distinguished from the other c subunits by their very short C-terminal cytoplasmic regions that lack functional motifs. (Chen )
Our current understanding of the cellular processes influenced by the gamma (c) subunits suggests a more diverse and complex range of regulatory functions than found with the other calcium channel auxiliary subunits. The gamma subunits interact not just with calcium channels but with other proteins as well. Principle cellular targets of several members of the calcium channel c subunit family may not be calcium channels at all. The first c subunit described, c1 (=cacng1), was isolated biochemically as a component of a calcium channel expressed in skeletal muscle and has been shown to alter calcium current properties in both native myocytes and in cell lines (Eberst , Freise , Held ). Historically, as additional members of this protein family were identified by sequence homology to c1, it was assumed that their functional roles were also homologous. It now seems clear that this assignment of common function may not have been appropriate. Four of the eight gamma subunits (c2, c3, c4, c8) are known to act as transmembrane AMPA receptor regulatory proteins (TARPs). Their major cellular function seems to be the regulation of trafficking and gating of AMPA receptors (Osten , X ). Thus the assumption that all c subunit proteins act primarily as regulators of calcium channel function is likely to be incorrect.
The founding member of the c subunit family, c1 (cacng1), was first isolated as a subunit of the high-voltage activated (HVA) calcium channel in skeletal muscle (Jay ). When co- expressed with the a1 subunit Cav1.2 in heterologous systems, c1 alters HVA calcium current kinetics and the voltage-dependency of inactivation (Eberst ), although a negative report demonstrating no effects of this subunit on calcium current has also been published (Chen ). The function of c1 has been studied in native skeletal muscle using the c1-null mouse (Arikkath , Freise , Held ) .