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

Abstract

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.

Residual body removal during spermatogenesis in C. elegans requires genes that mediate cell corpse clearance

“…Mutations in rab-14 and unc-108/RAB2 also caused defective residual body clearance, which was further enhanced in unc-108(n3263); rab-14(tm2095) double mutants (Fig. 3F,L), consistent with the redundant roles of UNC-108 and RAB-14 in regulating phagosome maturation Lu et al, 2008;Mangahas et al, 2008).…”

Drosophila Rab2 controls endosome-lysosome fusion and LAMP delivery to late endosomes

“…Interestingly, mammalian Rab2A has been found to promote LE exocytosis in cancer cells, suggesting that LE-plasma membrane fusion is also controlled by Rab2 [90]. The role of Rab2 in phagocytosis [42,43] likely parallels its function in the endolysosomal pathway, as the two pathways are mechanistically related. A LE-centric role of Rab2 in the endolysosomal pathway also explains why we do not detect any obvious perturbation of LRO formation in Rab2 null flies.…”

“…More recent data from C. elegans have demonstrated a role in the regulated secretory pathway, in the maturation of dense core vesicles [39–41]. In addition, Rab2 has a role in phagosome maturation [42–45]. In C. elegans , mutations in Rab2/UNC-108 impair progression through the conventional endolysosomal pathway at both early and late stages [46,47].…”

Integrative genome-wide association analysis of cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders

“…Although the exact biological function of RAB2A is not known in mammals, a recent study in Caenorhabditis elegans suggests that Rab2 protein is involved in regulation of locomotor activity and apoptosis depending on the cell type. 26 Apoptosis was one of the main processes associated with the density of calbindin-containing GABAergic neurons in our previous correlation analysis. 3 Akt1 mRNA and protein levels and MAPK1 mRNA levels were positively correlated with the density of calbindin-containing GABAergic neurons in our previous study, suggesting that deficits in Aktmediated antiapoptotic activity may be associated with the cytoarchitectural abnormality in psychiatric disorders.…”