Ubiquitination and proteasome-mediated degradation of voltage-gated Ca2+ channels and potential pathophysiological implications

Recent findings have revealed a fundamental role of the ubiquitin-proteasome system (UPS) in the regulation of voltage-gated Ca2+ channels (VGCCs). It has been proposed that the ubiquitination-deubiquitination balance dictates the number of channels expressed at the plasma membrane, which in turn influences a number of physiological and pathophysiological processes. This minireview surveys recent studies showing that VGCCs may be ubiquitinated in an unexpectedly complex manner, and highlights the role of the UPS in the regulation of the channels, focusing on the mechanisms that control their cell surface expression. The exciting new findings in this emerging field suggest that the turnover of VGCCs may be determined to a large degree by the activity of the UPS, and that alteration of the UPS molecular machinery may be one of the underlying mechanisms occurring in a number of channelopathies.