New roles for CaVβs subunits in the regulation of gene expression and cellular homeostasis

. Voltage-gated calcium channels (CaVs or VGCCs) regulate intracellular calcium homeostasis.

. Their activation by electrical activity leads to changes in intracellular Ca2+ levels regulating, depending on the cell type, various processes such as contraction, secretion and gene expression.

. While the CaVα1 subunit is the essential component of the calcium channel, the auxiliary β, α2δ, and γ subunits of CaVs play a modulatory role allowing fine regulation of Ca2+-dependent signals.

. In particular, there are four different CaVβ proteins (CaVβ1, CaVβ2, CaVβ3, and CaVβ4) that are encoded by four distinct genes in mammals, each with several splice variants. The function of some of these isoforms has been described: regulation of CaVα1 docking and stability at the membrane and control of conformational changes in the channel complex.

. Recent work has also identified other properties of CaVβs subunits that are independent of CaVα1 and are not related to its calcium channel modulatory or voltage sensing functions.

The authors, researchers at the Institute’s Myology Centre for Research in the group led by France Pietri-Rouxel “Gene Therapy for DMD & Skeletal Muscle Pathophysiology“, have compiled data from 49 articles in this review. They summarise the latest discoveries, including an important study published by their team, concerning the new roles of CaVβ auxiliary subunits, in particular their direct or indirect involvement in the regulation of gene expression in different cellular contexts.

 

New Insights in CaVβ Subunits: Role in the Regulation of Gene Expression and Cellular Homeostasis. Vergnol A, Traoré M, Pietri-Rouxel F, Falcone S. Front Cell Dev Biol. 2022 Apr 6;10:880441. doi: 10.3389/fcell.2022.880441. eCollection 2022. PMID: 35465309