Mangahas Paolo M, Yu Xiaomeng, Miller Kenneth G, Zhou Zheng
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
J Cell Biol. 2008 Jan 28;180(2):357-73. doi: 10.1083/jcb.200708130.
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.
我们在此鉴定出一类新的运动失调（unc）-108功能缺失等位基因，unc-108编码哺乳动物小GTP酶Rab2在秀丽隐杆线虫中的同源物。与先前分离出的显性负性突变体一样，unc-108功能缺失突变动物存在运动缺陷。此外，它们在清除凋亡细胞方面表现出独特的缺陷，揭示了Rab2以前未被描述的功能。unc-108分别在神经元和吞噬细胞中发挥作用，以控制运动和细胞尸体清除，这表明unc-108在不同细胞类型中具有不同的功能。通过延时显微镜观察，我们发现unc-108促进被吞噬细胞尸体的降解。它是溶酶体有效募集和融合到吞噬体以及吞噬体腔酸化所必需的。在吞噬细胞中，UNC-108在吞噬体表面富集。我们提出UNC-108作用于吞噬体表面以促进吞噬体成熟，并表明哺乳动物Rab2在凋亡细胞降解中可能具有类似功能。
