Presenilins: Role in calcium homeostasis
Presenilins: Role in calcium homeostasis
复制标题
DOI：
10.1016/j.biocel.2012.07.019
复制
发表时间：
2012-11-01
影响因子：
4
通讯作者：
Herms, Jochen
中科院分区：
文献类型：
--
作者：
Honarnejad, Kamran;Herms, Jochen
早老素突变是绝大多数早发家族性阿尔茨海默病病例的原因。全长早老素结构由位于内质网膜上的九个跨膜结构域组成。内切蛋白水解后，早老素组装成γ-分泌酶多蛋白复合物，随后被转运至细胞表面。关于早老素作为γ-分泌酶的催化成分的作用、它们参与淀粉样蛋白前体蛋白的加工和神经毒性β-淀粉样蛋白种类的产生，已有丰富的知识。然而，最近的研究结果揭示了多种不依赖于γ-分泌酶的早老素功能，包括参与钙稳态。特别是，家族性阿尔茨海默病早老素突变已被证明会干扰参与内质网钙稳态的几种分子元件的功能。早老素调节 IP3 和 Ryanodine 受体通道的活性，调节 SERCA 泵功能，影响电容性钙进入和功能本身作为内质网钙渗漏电导孔。 (c) 2012 年，爱思唯尔有限公司出版。
Mutations in presenilins are responsible for the vast majority of early-onset familial Alzheimer's disease cases. Full-length presenilin structure is composed of nine transmembrane domains which are localized on the endoplasmic reticulum membrane. Upon endoproteolytic cleavage, presenilins assemble into the gamma-secretase multiprotein complex and subsequently get transported to the cell surface. There is a wealth of knowledge around the role of presenilins as the catalytic component of gamma-secretase, their involvement in amyloid precursor protein processing and generation of neurotoxic beta-amyloid species. However recent findings have revealed a wide range of gamma-secretase-independent presenilin functions, including involvement in calcium homeostasis. Particularly, familial Alzheimer's disease presenilin mutations have been shown to interfere with the function of several molecular elements involved in endoplasmic reticulum calcium homeostasis. Presenilins modulate the activity of IP3 and Ryanodine receptor channels, regulate SERCA pump function, affect capacitative calcium entry and function per se as endoplasmic reticulum calcium leak conductance pores. (c) 2012 Published by Elsevier Ltd.