TMEM166, a novel transmembrane protein, regulates cell autophagy and apoptosis
TMEM166, a novel transmembrane protein, regulates cell autophagy and apoptosis
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TMEM166，一种新型跨膜蛋白，调节细胞自噬和凋亡
DOI：
10.1007/s10495-007-0073-9
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发表时间：
2007-08-01
期刊：
影响因子：
7.2
通讯作者：
Chen, Yingyu
中科院分区：
文献类型：
--
作者：
Wang, Lan;Yu, Chuanfei;Chen, Yingyu
细胞程序性死亡可分为细胞凋亡和自噬性细胞死亡。我们描述了TMEM 166（跨膜蛋白166，也称为FLJ 13391）的生物活性，TMEM 166是一种新的溶酶体和内质网相关的膜蛋白，含有一个假定的TM结构域。TMEM 166的过表达显著抑制HeLa细胞的集落形成。同时，透射电子显微镜观察到与自噬相符的典型形态学特征，包括广泛的自噬空泡化和细胞器被双膜结构包裹。进一步的实验证实，TMEM 166的过表达增加了HeLa细胞中MDC染色和GFP-LC 3的点状分布，以及LC 3-II/LC 3-I比例。另一方面，TMEM 166转染的HeLa和293 T细胞屈服于细胞死亡，具有凋亡的标志，包括磷脂酰丝氨酸外化、线粒体跨膜电位丧失、半胱天冬酶激活和染色质凝聚。动力学分析表明，自噬相关的生化参数的外观之前，典型的TMEM 166转染的HeLa细胞凋亡的核变化。通过小干扰RNA抑制TMEM 166的表达抑制了HeLa细胞中饥饿诱导的自噬。这些发现首次表明TMEM 166是一种参与自噬和凋亡的新型调节剂。
Programmed cell death can be divided into apoptosis and autophagic cell death. We describe the biological activities of TMEM166 (transmembrane protein 166, also known as FLJ13391), which is a novel lysosome and endoplasmic reticulum-associated membrane protein containing a putative TM domain. Overexpression of TMEM166 markedly inhibited colony formation in HeLa cells. Simultaneously, typical morphological characteristics consistent with autophagy were observed by transmission electron microscopy, including extensive autophagic vacuolization and enclosure of cell organelles by double-membrane structures. Further experiments confirmed that the overexpression of TMEM166 increased the punctate distribution of MDC staining and GFP-LC3 in HeLa cells, as well as the LC3-II/LC3-I proportion. On the other hand, TMEM166-transfected HeLa and 293T cells succumbed to cell death with hallmarks of apoptosis including phosphatidylserine externalization, loss of mitochondrial transmembrane potential, caspase activation and chromatin condensation. Kinetic analysis revealed that the appearance of autophagy-related biochemical parameters preceded the nuclear changes typical of apoptosis in TMEM166-transfected HeLa cells. Suppression of TMEM166 expression by small interference RNA inhibited starvation-induced autophagy in HeLa cells. These findings show for the first time that TMEM166 is a novel regulator involved in both autophagy and apoptosis.