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.

中文翻译：

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Neuroplastin和Basigin是血浆膜Ca2 + -ATPases的必需辅助亚基，是Ca2 +清除率的关键调节因子。

P型ATP酶家族的质膜Ca ²⁺ -ATPases（PMCAs）将Ca ²⁺离子从细胞质中挤出到细胞外空间，被认为是Ca ^2+的关键调节因子。信号。在这里，我们通过功能蛋白质组学表明，天然PMCA是异源复合物，由两个成孔的PMCA1-4亚基和两个单跨膜蛋白（神经质增生蛋白或基底蛋白）组装而成。两种含Ig结构域的蛋白质的贡献在不同类型的细胞之间以及随着出生后的发展而变化。内质网中会形成神经增塑剂或基底蛋白与PMCAs1-4的复合物，对于PMCA蛋白质的稳定性和PMCA复合物向表面膜的传递是必不可少的。神经增塑蛋白和basigin的敲除和（过）表达深刻影响PMCA介导的Ca ²⁺转运以及膜下Ca ²⁺的时间进程稳态条件下的浓度。在一起，这些结果建立了神经质促生长素和basigin作为天然PMCAs的强制性辅助亚基和细胞内Ca ²⁺浓度的关键调节剂。