Incretin-stimulated interaction between {beta}-cell Kv1.5 and Kv{beta}2 channel proteins involves acetylation/deacetylation by CBP/SirT1

The incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gastrointestinal hormones conferring a number of beneficial effects on β-cell secretion, survival and proliferation. In an earlier study, it was demonstrated that delayed rectifier channel protein Kv2.1 contributes to β-cell apoptosis and that prosurvival effects of incretins involve Kv2.1 post-translational modifications (PTMs), including phosphorylation and acetylation. Since Kv1.5 overexpression was also shown to stimulate β-cell death, the current study was initiated in order to determine whether incretins modulate Kv1.5α/Kvβ2 interaction via PTM and the mechanisms involved. GIP and GLP-1 reduced apoptosis in INS-1 (832/13) β-cells overexpressing Kv1.5, and RNAi-mediated knockdown of endogenous Kv1.5 attenuated apoptotic β-cell death. Both GIP and GLP-1 increased phosphorylation and acetylation of Kv1.5 and its Kvβ2 protein subunit, leading to their enhanced interaction. Further studies demonstrated that CREB binding protein (CBP)/Sirtuin deacetylase (SirT1) mediated acetylation/deacetylation and interaction between Kvβ2 and Kv1.5 in response to GIP/GLP-1. Incretin regulation of β-cell function therefore involves the acetylation of multiple Kvα and Kvβ subunits.
Source: BJ Signal - Category: Biochemistry Authors: Tags: BJ Metabolism Source Type: research