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

Sayaka Yasuda, So Morishita, Akane Fujita, Tomohisa Nanao, Naoyuki Wada, Satoshi Waguri, Giampietro Schiavo, Mitsunori Fukuda, Takeshi Nakamura

    Research output: Contribution to journalArticlepeer-review

    24 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)329-340
    Number of pages12
    JournalJournal of cell science
    Volume129
    Issue number2
    DOIs
    Publication statusPublished - 2016

    Keywords

    • Endolysosomal pathway
    • FRET
    • GEF
    • Small GTPase

    ASJC Scopus subject areas

    • Cell Biology

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