Journal
JOURNAL OF CELL SCIENCE
Volume 129, Issue 2, Pages 329-340Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.178095
Keywords
Small GTPase; FRET; Endolysosomal pathway; GEF
Categories
Funding
- Japan Society for the Promotion of Science [23300134, 24657094]
- Yamada Science Foundation: the Naito Foundation
- Hamaguchi Foundation for the Advancement of Biochemistry
- Grants-in-Aid for Scientific Research [15K06782, 25460254, 24657094, 23300134] Funding Source: KAKEN
Ask authors/readers for more resources
Rab GTPases act as molecular switches regulating various aspects of membrane trafficking. Among them, Rab5 and Rab7 play central roles in the endolysosomal network. Although many effectors downstream of Rab7 have been elucidated, our present understanding of the mechanism regulating Rab7 activity is extremely limited. It has only recently been accepted that the Mon1-Ccz1 complex is a Rab7 guanine nucleotide exchange factor, but it still remains unclear what the location where Mon1-Ccz1 works with Rab7 is. To address what kind of change or switch exists in the regulatory mechanism upstream of Rab7 during its transition from the late endosome to lysosome, we examined Rab7 activity in steady-state cells and during EGF-induced macropinocytosis using a newly developed FRET sensor. A combination of a Rab7 sensor and confocal FRET imaging techniques revealed that the activation of Rab7 on late endosomes depends on Mon1-Ccz1 and is implicated in late-endosome-lysosome fusion. In contrast, Rab7 activity on lysosomes was independent of Mon1-Ccz1 and active Rab7 played a role in perinuclear clustering of lysosomes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available