Abstract
Endolysosomal system is linked to almost all aspects of a cell’s life and diseases, and Rab7 occupies a critical node in this endocytic degradation pathway. However, there have been conflicting theories about the exact role of Rab7 in membrane trafficking, since some researchers report that Rab7 regulates the trafficking from early to late endosomes, while others have reported its functions in trafficking between late endosomes to lysosomes. In the present study, we have revisited this issue from a new perspective. In COS-7 cells, the GDP-bound Rab7 mutant, T22N, was found to be located on the vesicular membranes as well as in the cytoplasm. On the other hand, the GTPase-deficient Q67L mutant of Rab7 resided in cytoplasm as well as on membranes. Additionally, we found that RabGDI interacted with both GTP and GDP bound forms of Rab7 in vitro. Based on the results we have proposed a four-state transition model for Rab7. This four-state model correlates with our recent findings that Rab7 was initially recruited to macropinosomes in a GDP-bound inactive form and subsequently activated during endocytic maturation in EGF-stimulated COS-7 cells.