New Ca(2+)-dependent regulators of autophagosome maturation.
New Ca(2+)-dependent regulators of autophagosome maturation.
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DOI：
10.4161/cib.20076
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发表时间：
2012-07-01
影响因子：
--
通讯作者：
Knecht E
中科院分区：
文献类型：
--
作者：
Ghislat G;Knecht E
自噬是一种膜运输途径，负责分解细胞内不需要的物质，对细胞的健康和生存至关重要。在自噬通量中，各种动态的膜重排发生，从吞噬体的延伸和关闭开始，形成自噬体，到与晚期内体和溶酶体融合形成自噬体结束。虽然Ca2+是一个公认的膜融合事件的调节剂，但它在自噬过程中的作用知之甚少。最近基于溶酶体膜蛋白质组学分析的研究为这一研究领域提供了新的见解。因此，溶酶体膜上膜联蛋白A1、膜联蛋白A5和copine 1的水平在营养剥夺下增加，这三种蛋白以Ca2+依赖的方式与磷脂膜结合，这是一种促进自噬降解的条件。此外，两项不同的研究表明，膜联蛋白A5和膜联蛋白A1参与自噬体成熟。在这里，我们讨论了自噬体与核内体和溶酶体的融合可以通过这三种蛋白质和Ca2+调节的分子机制。
Autophagy is a membrane trafficking pathway responsible for the breakdown of unwanted intracellular materials and crucial for the cell healthiness and survival. In the autophagic flux, various dynamic membrane rearrangements occurs starting with the elongation of the phagophore and its closure to build an autophagosome and ending with its fusion with late endosomes and lysosomes to form an autolysosome. Although Ca2+ is a well established regulator of membrane fusion events, little is known about its role in these processes during autophagy. Recent studies, based on proteomic analyses of lysosomal membranes, have provided new insights into this field of study. Thus, the levels on lysosomal membranes of annexin A1, annexin A5 and copine 1, three proteins that bind to phospholipid membranes in a Ca2+-dependent manner, increased under nutrient deprivation, a condition that promotes autophagic degradation. In addition, two different studies showed that annexin A5 and annexin A1 are involved in autophagosome maturation. Here, we discuss the molecular mechanisms by which the fusion of autophagosomes with endosomes and lysosomes could be regulated by these three proteins and Ca2+.