Primeau Joseph O, Armanious Gareth P, Fisher M'Lynn E, Young Howard S
Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
Subcell Biochem. 2018;87:229-258. doi: 10.1007/978-981-10-7757-9_8.
The calcium pump (a.k.a. Ca-ATPase or SERCA) is a membrane transport protein ubiquitously found in the endoplasmic reticulum (ER) of all eukaryotic cells. As a calcium transporter, SERCA maintains the low cytosolic calcium level that enables a vast array of signaling pathways and physiological processes (e.g. synaptic transmission, muscle contraction, fertilization). In muscle cells, SERCA promotes relaxation by pumping calcium ions from the cytosol into the lumen of the sarcoplasmic reticulum (SR), the main storage compartment for intracellular calcium. X-ray crystallographic studies have provided an extensive understanding of the intermediate states that SERCA populates as it progresses through the calcium transport cycle. Historically, SERCA is also known to be regulated by small transmembrane peptides, phospholamban (PLN) and sarcolipin (SLN). PLN is expressed in cardiac muscle, whereas SLN predominates in skeletal and atrial muscle. These two regulatory subunits play critical roles in cardiac contractility. While our understanding of these regulatory mechanisms are still developing, SERCA and PLN are one of the best understood examples of peptide-transporter regulatory interactions. Nonetheless, SERCA appeared to have only two regulatory subunits, while the related sodium pump (a.k.a. Na, K-ATPase) has at least nine small transmembrane peptides that provide tissue specific regulation. The last few years have seen a renaissance in our understanding of SERCA regulatory subunits. First, structures of the SERCA-SLN and SERCA-PLN complexes revealed molecular details of their interactions. Second, an array of micropeptides concealed within long non-coding RNAs have been identified as new SERCA regulators. This chapter will describe our current understanding of SERCA structure, function, and regulation.
钙泵（又称Ca - ATP酶或肌浆网钙ATP酶）是一种膜转运蛋白，普遍存在于所有真核细胞的内质网（ER）中。作为一种钙转运蛋白，肌浆网钙ATP酶维持着细胞质中低钙水平，这使得大量的信号通路和生理过程（如突触传递、肌肉收缩、受精）得以进行。在肌肉细胞中，肌浆网钙ATP酶通过将钙离子从细胞质泵入肌浆网（SR）腔来促进肌肉松弛，肌浆网是细胞内钙的主要储存区。X射线晶体学研究使我们对肌浆网钙ATP酶在钙转运循环过程中所经历的中间状态有了广泛的了解。从历史上看，肌浆网钙ATP酶也已知受小跨膜肽、受磷蛋白（PLN）和肌浆脂蛋白（SLN）的调节。受磷蛋白在心肌中表达，而肌浆脂蛋白在骨骼肌和心房肌中占主导。这两个调节亚基在心脏收缩性中起关键作用。虽然我们对这些调节机制的理解仍在不断发展，但肌浆网钙ATP酶和受磷蛋白是肽 - 转运蛋白调节相互作用中理解得最好的例子之一。尽管如此，肌浆网钙ATP酶似乎只有两个调节亚基，而相关的钠泵（又称钠钾ATP酶）有至少九个小跨膜肽，可提供组织特异性调节。在过去几年里，我们对肌浆网钙ATP酶调节亚基的理解有了复兴。首先，肌浆网钙ATP酶 - 肌浆脂蛋白和肌浆网钙ATP酶 - 受磷蛋白复合物的结构揭示了它们相互作用的分子细节。其次，一系列隐藏在长链非编码RNA中的微小肽已被鉴定为新的肌浆网钙ATP酶调节因子。本章将描述我们目前对肌浆网钙ATP酶的结构、功能和调节的理解。
