Posttranscriptional and Posttranslational Regulation of BK Channels

Large conductance calcium- and voltage-activated potassium (BK) channels are ubiquitously expressed and play an important role in the regulation of an eclectic array of physiological processes. Their diverse functional role requires channels with a wide variety of properties even though the pore-forming alpha-subunit is encoded by a single gene, KCNMA1. To achieve this, BK channels exploit some of the most fundamental posttranscriptional and posttranslational mechanisms that allow proteomic diversity to be generated from a single gene. These include mechanisms that diversify mRNA variants and abundance such as alternative pre-mRNA splicing, editing, and control by miRNA. The BK channel is also subject to a diverse array of posttranslational modifications including protein phosphorylation, lipidation, glycosylation, and ubiquitination to control the number, properties, and regulation of BK channels in specific cell types. Importantly, "cross talk" between these posttranscriptional and posttranslational modifications typically converge on disordered domains of the BK channel alpha-subunit. This allows both wide physiological diversity to be generated and a diversity of mechanisms to allow conditional regulation of BK channels and is emerging as an important determinant of BK channel function in health and disease.