リソソームにおける低分子量Gタンパク質Arl8の機能解析

抄録

Arl8 is the first Arf-like GTPase found to be localized to lysosomes and a highly conserved GTPase in multi-cellular organisms. In the present study, we analyzed possible role(s) of Arl8 in lysosome biogenesis and functions using C. elegans. We isolated loss-of-function mutants for arl-8 and found that the individual late endosomes and/or lysosomes got smaller with the increasing number of these vesicles in the coelomocytes (macrophage-like scavenger cells in C. elegans) of arl-8 mutants. arl-8 mutants also showed that endocytosed macromolecules, which are efficiently degraded in lysosomes of wild-type coelomocytes, are abnormally accumulated in late endosomes of arl-8 mutants. These results suggest that arl-8 is required for trafficking from late endosomes to lysosomes. Recent research has suggested that lysosomes can fuse with late endosomes, leading to the formation of an endosome-lysosome hybrid organelle; however, the molecular mechanisms underlying the hybrid-organelle formation remain unresolved. cup-5, the C. elegans mucolipin-1 homolog, functions in the reformation of lysosomes from endosome-lysosome hybrid organelles. We found that the enlarged hybrid-organelle formation in cup-5 mutants is strongly suppressed by null mutations in arl-8, indicating that arl-8 acts genetically upstream of cup-5. Collectively, these results suggest that arl-8 positively regulates the hybrid-organelle formation between late endosomes and lysosomes. [J Physiol Sci. 2008;58 Suppl:S25]