Béguin et al. identify a new protein that curbs the activity of voltage-gated calcium channels, which prompt everything from muscle contraction to hormone release.
By allowing calcium to pour into cells, voltage-gated calcium channels trigger a variety of responses. The calcium surge spurs neurons to release neurotransmitters, for instance, and induces pancreatic islet cells to secrete insulin. A core component, the Cavα1 subunit, combines with several other subunits, including Cavβ, to form the channels. Keeping the channels under tight control is crucial because excess calcium can kill cells. Researchers have identified a number of proteins that adjust the activity of the channels by latching onto Cavα1 and Cavβ.
Béguin et al. uncovered another regulator, which they dubbed BARP, when they searched for proteins that attach to one variant of Cavβ. BARP is expressed in several tissues, including the brain and pancreas, and two sections of the protein, domains I and II, can bind to Cavβ.
The researchers discovered that BARP dials down the activity of calcium channels but doesn’t affect channel abundance at the cell surface. When they dosed adrenal gland cells with siRNAs that target BARP, they found that the treatment almost doubled release of the neurotransmitter acetylcholine. The researchers think that BARP works by separating the Cavβ and Cavα1subunits, thereby shutting down the channels. One question they want to pursue is whether BARP is mutated in channelopathies, diseases in which calcium channels malfunction.
Text by Mitch Leslie