The small GTPase Rab2 functions in the removal of apoptotic cells in Caenorhabditis elegans.

The small GTPase Rab2 functions in the removal of apoptotic cells in Caenorhabditis elegans.
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DOI:
10.1083/jcb.200708130
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发表时间:
2008-01-28
影响因子:
7.8
通讯作者:
Zhou, Zheng
Zhou, Zheng
中科院分区:
生物学1区
文献类型:
--
作者:
Mangahas, Paolo M.;Yu, Xiaomeng;Miller, Kenneth G.;Zhou, Zheng

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我们在这里发现了一类新的非协调运动(UNC)功能缺失等位基因-108,它编码哺乳动物小鸟苷三磷酸酶Rab2的秀丽线虫同源物。与之前分离的显性-负性突变体一样,UNC-108功能丧失突变动物的运动能力也存在缺陷。此外,它们在去除凋亡细胞方面表现出独特的缺陷,揭示了Rab2以前未描述的功能。UNC-108分别作用于神经元和吞噬细胞,分别控制运动和细胞身体的移动,表明UNC-108在不同的细胞类型中具有不同的功能。利用延时显微镜,我们发现UNC-108促进了吞噬细胞身体的降解。它是有效地将溶酶体招募和融合到吞噬体内以及吞噬体腔的酸化所必需的。在吞噬细胞中,UNC-108富含在吞噬小体表面。我们推测UNC-108作用于吞噬小体表面促进吞噬小体成熟,并提示哺乳动物Rab2在降解凋亡细胞方面可能具有类似的功能。
We identify here a novel class of loss-of-function alleles of uncoordinated locomotion (unc)-108, which encodes the Caenorhabditis elegans homologue of the mammalian small guanosine triphosphatase Rab2. Like the previously isolated dominant-negative mutants, unc-108 loss-of-function mutant animals are defective in locomotion. In addition, they display unique defects in the removal of apoptotic cells, revealing a previously uncharacterized function for Rab2. unc-108 acts in neurons and engulfing cells to control locomotion and cell corpse removal, respectively, indicating that unc-108 has distinct functions in different cell types. Using time-lapse microscopy, we find that unc-108 promotes the degradation of engulfed cell corpses. It is required for the efficient recruitment and fusion of lysosomes to phagosomes and the acidification of the phagosomal lumen. In engulfing cells, UNC-108 is enriched on the surface of phagosomes. We propose that UNC-108 acts on phagosomal surfaces to promote phagosome maturation and suggest that mammalian Rab2 may have a similar function in the degradation of apoptotic cells.
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