The plasma membrane calcium pumps: focus on the role in (neuro) pathology
The plasma membrane calcium pumps: focus on the role in (neuro) pathology
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DOI：
10.1016/j.bbrc.2016.07.117
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发表时间：
2017-02-19
影响因子：
3.1
通讯作者：
Cali, Tito
中科院分区：
文献类型：
--
作者：
Brini, Marisa;Carafoli, Ernesto;Cali, Tito
质膜Ca 2 + ATP酶（PMCA泵）是P型泵超家族的成员。它在质膜上有十个跨膜螺旋和两个主要的胞质环，其中一个含有催化中心。它还包含一个长的C-末端尾巴，容纳钙调蛋白的结合位点，钙调蛋白是泵活性的主要调节剂。该泵还包含许多其他调节剂，其中包括酸性磷脂、激酶和许多蛋白质相互作用物。在哺乳动物中，单独的基因编码4种基本的泵亚型，通过初级转录物的选择性剪接产生额外的亚型复杂性。泵1和4普遍表达，泵2和3是组织限制性的，优选神经系统。在基本上所有的细胞中，泵与更强大的系统共存，这些系统从细胞质中清除Ca 2+，例如SERCA泵和Na+/Ca 2+交换器。因此，其在细胞Ca 2+稳态的全局调节中的作用在数量上是边缘的：其主要功能是在选定的质膜下微区中调节Ca 2+信号，其中Ca 2+调节的相互作用物也存在。与基因突变有关的泵的故障现在被描述的频率越来越高，疾病表型在神经系统中特别严重，其中亚型2和3占主导地位。泵缺陷的分析表明，疾病表型可能与选定的质膜下微区中的Ca 2+信号转导的不完善调节有关，导致重要的Ca 2+依赖性相互作用物的活性的缺陷控制。(C)2016 Elsevier Inc. All rights reserved.
The plasma membrane Ca2+ ATPase (PMCA pump) is a member of the superfamily of P-type pumps. It is organized in the plasma membrane with ten transmembrane helices and two main cytosolic loops, one of which contains the catalytic center. It also contains a long C-terminal tail that houses the binding site for calmodulin, the main regulator of the activity of the pump. The pump also contains a number of other regulators, among them acidic phospholipids, kinases, and numerous protein interactors. Separate genes code for 4 basic pump isoforms in mammals, additional isoform complexity being generated by the alternative splicing of primary transcripts. Pumps 1 and 4 are expressed ubiquitously, pumps 2 and 3 are tissue restricted, with preference for the nervous system. In essentially all cells, the pump coexists with much more powerful systems that clear Ca2+ from the cytosol, e.g. the SERCA pump and the Na+/Ca2+ exchanger. Its role in the global regulation of cellular Ca2+ homeostasis is thus quantitatively marginal: its main function is the regulation of Ca2+ signaling in selected sub-plasma membrane microdomains where Ca2+ modulated interactors also reside. Malfunctions of the pump linked to genetic mutations are now described with increasing frequency, the disease phenotypes being especially severe in the nervous system where isoforms 2 and 3 predominate. The analysis of the pump defects suggests that the disease phenotypes are likely to be related to the imperfect modulation of Ca2+ signaling in selected sub-plasma membrane microdomains, leading to the defective control of the activity of important Ca2+ dependent interactors. (C) 2016 Elsevier Inc. All rights reserved.