RRC ID |
61901
|
著者 |
Yasuda S, Morishita S, Fujita A, Nanao T, Wada N, Waguri S, Schiavo G, Fukuda M, Nakamura T.
|
タイトル |
Mon1-Ccz1 activates Rab7 only on late endosomes and dissociates from the lysosome in mammalian cells.
|
ジャーナル |
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.
|
巻・号 |
129(2)
|
ページ |
329-40
|
公開日 |
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
|
リソース情報 |
遺伝子材料 |
pEGFP-C1-mouse Mon1a (RDB15294)
pEGFP-C1-mouse Ccz1 (RDB15295) |