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标题：Rab11-dependent recycling of calcium channels is mediated by auxiliary subunit α ₂δ-1 but not α ₂δ-3
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作者：James O. Meyer ; Annette C. Dolphin
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2021
卷号：11
DOI：10.1038/s41598-021-89820-1
语种：English
出版社：Springer Nature
摘要：N-type voltage-gated calcium channels (Ca V2.2) are predominantly expressed at presynaptic terminals, and their function is regulated by auxiliary α 2δ and β subunits. All four mammalian α 2δ subunits enhance calcium currents through Ca V1 and Ca V2 channels, and this increase is attributed, in part, to increased Ca V expression at the plasma membrane. In the present study we provide evidence that α 2δ-1, like α 2δ-2, is recycled to the plasma membrane through a Rab11a-dependent endosomal recycling pathway. Using a dominant-negative Rab11a mutant, Rab11a(S25N), we show that α 2δ-1 increases plasma membrane Ca V2.2 expression by increasing the rate and extent of net forward Ca V2.2 trafficking in a Rab11a-dependent manner. Dominant-negative Rab11a also reduces the ability of α 2δ-1 to increase Ca V2.2 expression on the cell-surface of hippocampal neurites. In contrast, α 2δ-3 does not enhance rapid forward Ca V2.2 trafficking, regardless of whether Rab11a(S25N) is present. In addition, whole-cell Ca V2.2 currents are reduced by co-expression of Rab11a(S25N) in the presence of α 2δ-1, but not α 2δ-3. Taken together these data suggest that α 2δ subtypes participate in distinct trafficking pathways which in turn influence the localisation and function of Ca V2.2.