RRC ID 61901
Author Yasuda S, Morishita S, Fujita A, Nanao T, Wada N, Waguri S, Schiavo G, Fukuda M, Nakamura T.
Title Mon1-Ccz1 activates Rab7 only on late endosomes and dissociates from the lysosome in mammalian cells.
Journal J Cell Sci
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.
Volume 129(2)
Pages 329-40
Published 2016-1-15
DOI 10.1242/jcs.178095
PII jcs.178095
PMID 26627821
MeSH Animals COS Cells Chlorocebus aethiops Endosomes / enzymology* Enzyme Activation HEK293 Cells HeLa Cells Humans Lysosomes / enzymology* Metabolic Networks and Pathways Protein Transport Vesicular Transport Proteins / metabolism* rab GTP-Binding Proteins / metabolism* rab7 GTP-Binding Proteins
IF 4.573
DNA material pEGFP-C1-mouse Mon1a (RDB15294) pEGFP-C1-mouse Ccz1 (RDB15295)