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Published online January 28, 2008
doi:10.1083/jcb.200708130
The Journal of Cell Biology, Vol. 180, No. 2, 357-373
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Mangahas et al.
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Article

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

Paolo M. Mangahas1, Xiaomeng Yu2, Kenneth G. Miller3, and Zheng Zhou1,2

1 Program in Developmental Biology and 2 Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030
3 Program in Molecular, Cell and Developmental Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104

Correspondence to Z. Zhou: zhengz{at}bcm.tmc.edu

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.

Abbreviations used in this paper: Ced, cell death abnormal; DIC, differential interference contrast; DYN-1, dynamin 1; HGRS-1, hepatocyte growth factor–regulated tyrosine kinase substrate; mRFP1, monomeric RFP 1; PI(3)P, phosphatidylinositol-3-monophosphate; TEM, transmission EM; Unc, uncoordinated locomotion.


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