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Mon1-Ccz1 activates Rab7 only on late endosomes and dissociates from the lysosome in mammalian cells

Yasuda, S; Morishita, S; Fujita, A; Nanao, T; Wada, N; Waguri, S; Schiavo, G; ... Nakamura, T; + view all (2016) Mon1-Ccz1 activates Rab7 only on late endosomes and dissociates from the lysosome in mammalian cells. Journal of Cell Science , 129 (2) pp. 329-340. 10.1242/jcs.178095. Green open access

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Abstract

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.

Type: Article
Title: Mon1-Ccz1 activates Rab7 only on late endosomes and dissociates from the lysosome in mammalian cells
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/jcs.178095
Publisher version: http://dx.doi.org/10.1242/jcs.178095
Language: English
Additional information: Copyright © 2016. Published by The Company of Biologists Ltd.
Keywords: Endolysosomal pathway, FRET, GEF, Small GTPase
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1488914
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