Apocalmodulin Itself Promotes Ion Channel Opening and Ca2+ Regulation

作者：Adams Paul J; Ben Johny Manu; Dick Ivy E; Inoue Takanari; Yue David T^*

来源：Cell, 2014, 159(3): 608-622.

DOI：10.1016/j.cell.2014.09.047

The Ca2+-free form of calmodulin (apoCaM) often appears inert, modulating target molecules only upon conversion to its Ca2+-bound form. This schema has appeared to govern voltage-gated Ca2+ channels, where apoCaM has been considered a dormant Ca2+ sensor, associated with channels but awaiting the binding of Ca2+ ions before inhibiting channel opening to provide vital feedback inhibition. Using single-molecule measurements of channels and chemical dimerization to elevate apoCaM, we find that apoCaM binding on its own markedly upregulates opening, rivaling the strongest forms of modulation. Upon Ca2+ binding to this CaM, inhibition may simply reverse the initial upregulation. As RNA-edited and - spliced channel variants show different affinities for apoCaM, the apoCaM-dependent control mechanisms may underlie the functional diversity of these variants and explain an elongation of neuronal action potentials by apoCaM. More broadly, voltage-gated Na channels adopt this same modulatory principle. ApoCaM thus imparts potent and pervasive ion-channel regulation.

• 出版日期2014-10-23