细胞凋亡是发育中的一个重要环节。其中凋亡细胞的清除能防止凋亡细胞中的有害物质外泄而伤害正常细胞，凋亡细胞清除缺陷会导致炎症和免疫紊乱。2009年6月23日，北京生命科学研究所王晓晨实验室在Development杂志在线发表有关GTP水解激活蛋白TBC-2在凋亡细胞清除过程中功能的最新研究成果。
研究以线虫为模式生物，通过遗传筛选获得凋亡细胞清除异常突变体，并将其所影响基因tbc-2克隆，tbc-2编码一个具有TBC结构RAB GTPase的GAP。TBC-2具有3个结构：PH, SMC和TBC。根据结构缺失分析，表明这三个结构对于TBC-2发挥凋亡细胞清除功能都是不可或缺的。其中SMC结构负责将TBC-2定位在吞噬体上。TBC-2的GAP活性的破坏会造成TBC-2彻底失去凋亡细胞清除功能，表明TBC-2的GAP活性对于凋亡细胞降解是必须的。
研究发现rab-5 RNAi可以缓解tbc-2突变体中凋亡细胞降解的缺陷，同时过表达持久激活的RAB-5也会造成类似于tbc-2突变体中凋亡细胞降解的缺陷，表明在凋亡细胞降解的过程中，TBC-2可能调控RAB-5。
为了进一步了解TBC-2是如何通过调节RAB-5进而调控凋亡细胞降解过程，研究人员在tbc-2突变体中追踪了RAB-5在吞噬体上的动态分布，发现在突变体中RAB-5从吞噬体上的释放被延迟了，同时发现吞噬体对RAB-7的募集，吞噬体与溶酶体的融合，以及吞噬体的酸化都受到了影响，表明TBC-2在吞噬体上可以下调RAB-5的活性，促使RAB-5从吞噬体上释放，进而促进吞噬体进一步成熟。（生物谷Bioon.com）
生物谷推荐原始出处：
Development 136, 2445-2455 (2009) doi: 10.1242/10.1242/dev.035949
C. elegans Rab GTPase activating protein TBC-2 promotes cell corpse degradation by regulating the small GTPase RAB-5
Weida Li1,3, Wei Zou2,3, Dongfeng Zhao3, Jiacong Yan3, Zuoyan Zhu1, Jing Lu3 and Xiaochen Wang3,*
1 College of Life Science, Peking University, Beijing 100871, China.
2 College of Biological Sciences, China Agricultural University, Beijing 100094, China.
3 National Institute of Biological Sciences, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China.
During apoptosis, dying cells are quickly internalized by neighboring cells or phagocytes, and are enclosed in phagosomes that undergo a maturation process to generate the phagoslysosome, in which cell corpses are eventually degraded. It is not well understood how apoptotic cell degradation is regulated. Here we report the identification and characterization of the C. elegans tbc-2 gene, which is required for the efficient degradation of cell corpses. tbc-2 encodes a Rab GTPase activating protein (GAP) and its loss of function affects several events of phagosome maturation, including RAB-5 release, phosphatidylinositol 3-phosphate dynamics, phagosomal acidification, RAB-7 recruitment and lysosome incorporation, which leads to many persistent cell corpses at various developmental stages. Intriguingly, the persistent cell corpse phenotype of tbc-2 mutants can be suppressed by reducing gene expression of rab-5, and overexpression of a GTP-locked RAB-5 caused similar defects in phagosome maturation and cell corpse degradation. We propose that TBC-2 functions as a GAP to cycle RAB-5 from an active GTP-bound to an inactive GDP-bound state, which is required for maintaining RAB-5 dynamics on phagosomes and serves as a switch for the progression of phagosome maturation.
