Plasma membrane Ca2+-ATPase: from a housekeeping function to a versatile signaling role
Plasma membrane Ca2+-ATPase: from a housekeeping function to a versatile signaling role
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DOI：
10.1007/s00424-008-0505-6
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发表时间：
2009-01-01
影响因子：
4.5
通讯作者：
Brini, Marisa
中科院分区：
文献类型：
--
作者：
Brini, Marisa
质膜Ca ~（2+）-ATP酶（Plasma membrane Ca ~（2+）-ATP ases，PMCAs）是一种高亲和力的钙泵，通过将Ca ~（2+）从细胞质输出到细胞外环境，维持细胞内Ca ~（2+）的稳态。哺乳动物有四个基因编码蛋白质PMCA 1至PMCA 4。每个基因转录物被选择性剪接以产生几个变体。它们的分布是组织和细胞特异性的，并在细胞发育和分化过程中受到调节。传统上，这些泵被认为在控制基础Ca 2+水平方面发挥管家作用，但最近，很明显，不同亚型的存在（和共表达）必须与更专门的功能有关。四个基因中只有一个（编码PMCA 2）与哺乳动物的疾病有因果关系：几个自发突变导致耳聋和共济失调。其他复杂的人类疾病表型，如听力损失，心脏功能和不孕症可能与PMCA功能有关，但迄今为止，除PMCA 2外，还没有发现其他PMCA基因的自发突变。它们参与疾病表型的证据来自对同种型特异性敲除小鼠的研究。在这篇综述中，我将简要地讨论PMCA作为Ca 2+稳态机制的重要组成部分的一般作用，并专注于其作为信号分子的新兴作用，特别关注PMCA功能障碍引起的疾病。
Plasma membrane Ca2+-ATPases (PMCAs) are high-affinity calcium pumps that contribute to the maintenance of intracellular Ca2+ homeostasis by exporting Ca2+ from the cytosol to the extracellular environment. Mammals have four genes encoding the proteins PMCA1 through PMCA4. Each gene transcript is alternatively spliced to generate several variants. Their distribution is tissue- and cell-specific and undergoes regulation during cell development and differentiation. Traditionally, these pumps have been considered to play a housekeeping role in controlling basal Ca2+ levels, but more recently, it became clear that the presence (and the co-expression) of different isoforms must be related to a more specialized function. Only one of the four genes (encoding PMCA2) has been causally linked to disease in mammals: Several spontaneous mutations are responsible for deafness and ataxia. Other complex human disease phenotype like hearing loss, cardiac function, and infertility are likely to be associated with PMCA function, but no spontaneous mutations in other PMCA genes than PMCA2 are so far identified. The evidence of their involvement in disease phenotypes comes from studies on isoform-specific knockout mice. In this review, I will discuss briefly the general role of PMCA as essential component of Ca2+ homeostasis machinery and focus on its emerging role as signaling molecule with particular attention on the diseases caused by PMCA dysfunction.