Jurisch-Yaksi Nathalie, Sannerud Ragna, Annaert Wim
Laboratory for Membrane Trafficking, VIB-Center for the Biology of Disease & Department for Human Genetics (KU Leuven), Leuven, Belgium.
Biochim Biophys Acta. 2013 Dec;1828(12):2815-27. doi: 10.1016/j.bbamem.2013.04.016.
γ-secretase, which assembles as a tetrameric complex, is an aspartyl protease that proteolytically cleaves substrate proteins within their membrane-spanning domain; a process also known as regulated intramembrane proteolysis (RIP). RIP regulates signaling pathways by abrogating or releasing signaling molecules. Since the discovery, already >15 years ago, of its catalytic component, presenilin, and even much earlier with the identification of amyloid precursor protein as its first substrate, γ-secretase has been commonly associated with Alzheimer's disease. However, starting with Notch and thereafter a continuously increasing number of novel substrates, γ-secretase is becoming linked to an equally broader range of biological processes. This review presents an updated overview of the current knowledge on the diverse molecular mechanisms and signaling pathways controlled by γ-secretase, with a focus on organ development, homeostasis and dysfunction. This article is part of a Special Issue entitled: Intramembrane Proteases.
γ-分泌酶组装成四聚体复合物，是一种天冬氨酸蛋白酶，可在跨膜结构域内对底物蛋白进行蛋白水解切割；这一过程也称为调节性膜内蛋白水解（RIP）。RIP通过消除或释放信号分子来调节信号通路。自从15年前发现其催化成分早老素以来，甚至更早之前将淀粉样前体蛋白鉴定为其首个底物，γ-分泌酶一直与阿尔茨海默病密切相关。然而，从Notch开始，随后新底物的数量不断增加，γ-分泌酶正与同样广泛的生物过程联系在一起。本综述对γ-分泌酶所控制的多种分子机制和信号通路的当前知识进行了更新概述，重点关注器官发育、稳态和功能障碍。本文是名为“膜内蛋白酶”的特刊的一部分。
