Neuroplastin and Basigin Are Essential Auxiliary Subunits of Plasma Membrane Ca2+-ATPases and Key Regulators of Ca2+ Clearance
Neuroplastin and Basigin Are Essential Auxiliary Subunits of Plasma Membrane Ca2+-ATPases and Key Regulators of Ca2+ Clearance
复制标题
DOI：
10.1016/j.neuron.2017.09.038
复制
发表时间：
2017-11-15
期刊：
影响因子：
16.2
通讯作者：
Schulte, Uwe
中科院分区：
文献类型：
--
作者：
Schmidt, Nadine;Kollewe, Astrid;Schulte, Uwe
质膜Ca ~（2+）-ATP酶（Plasma membrane Ca ~（2+）-ATP酶，PMCAs）是一个P型ATP酶家族，能将Ca ~（2+）从细胞质中挤出到细胞外空间，被认为是Ca ~（2+）信号转导的关键调节因子。在这里，我们通过功能蛋白质组学表明，天然PMCA是由两个成孔PMCA 1 -4亚基和两个单跨膜蛋白（neuroplastin或basigin）组装而成的异聚复合物。这两种含有IG结构域的蛋白质的贡献在不同类型的细胞和沿着出生后发育中变化。在内质网中发生神经质蛋白或basigin与PMCAs 1 -4的复合物形成，并且对于PMCA蛋白的稳定性和PMCA复合物向表面膜的递送是必需的。敲除和（过度）表达的neuropastin和basigin深刻影响的时间过程中的PMCA介导的Ca 2+运输，以及在稳态条件下的膜下Ca 2+浓度。总之，这些结果建立neuroplastin和basigin作为强制性的辅助亚基的天然PMCAs和细胞内Ca 2+浓度的关键调节剂。
Plasma membrane Ca2+-ATPases (PMCAs), a family of P-type ATPases, extrude Ca2+ ions from the cytosol to the extracellular space and are considered to be key regulators of Ca2+ signaling. Here we show by functional proteomics that native PMCAs are heteromeric complexes that are assembled from two pore-forming PMCA1-4 subunits and two of the single-span membrane proteins, either neuroplastin or basigin. Contribution of the two Ig domain-containing proteins varies among different types of cells and along postnatal development. Complex formation of neuroplastin or basigin with PMCAs1-4 occurs in the endoplasmic reticulum and is obligatory for stability of the PMCA proteins and for delivery of PMCA complexes to the surface membrane. Knockout and (over)-expression of both neuroplastin and basigin profoundly affect the time course of PMCA-mediated Ca2+ transport, as well as submembraneous Ca2+ concentrations under steady-state conditions. Together, these results establish neuroplastin and basigin as obligatory auxiliary subunits of native PMCAs and key regulators of intracellular Ca2+ concentration.