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Control of RAB7 activity and localization through the retromer-TBC1D5 complex enables RAB7-dependent mitophagy

Jimenez‐Orgaz, Ana, Kvainickas, Arunas, Nägele, Heike, Denner, Justin, Eimer, Stefan, Dengjel, Jörn, Steinberg, Florian·2018·The EMBO Journal
DOI 10.15252/embj.201797128PMC PMC5770787
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Crossref · 10.15252/embj.201797128

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  • Loss of retromer leads to impaired mTORC1 activity, induction of autophagy, and the appearance of swollen and evenly dispersed lysosomes.

    “This leads to impaired mTORC1 activity and the induction of autophagy, and the appearance of swollen and evenly dispersed lysosomes (Jimenez-Orgaz et al., 2018; Cui et al., 2019; Curnock et al., 2019; Kvainickas et al., 2019).”

    From Acute inactivation of retromer and ESCPE-1 leads to time-resolved defects in endosomal cargo sorting (2020) · cites this paper as Jimenez-Orgaz et al., 2018

  • The Retromer sub-domain proximity proteome included the RAB7 GAP TBC1D5, the RAB21/RAB32/RAB38 GEF VARP, and the RAB10 GEFs DENND4A and DENND4C.

    “These included known Retromer accessory proteins, the RAB7 GAP TBC1D546,77–81, the RAB21/RAB32/RAB38 GEF VARP (a.k.a. ANKRD27)47,48,82, and the RAB10 GEFs DENND4A and DENND4C83,84.”

    From Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation (2025) · cites this paper as [80]

  • In the absence of retromer, RAB7 loses its dynamic organisation on endosomes and lysosomes and becomes hyperactivated and immobile on lysosomes.

    “In the absence of retromer, RAB7 loses its dynamic organisation on endosomes and lysosomes and becomes hyperactivated and immobile on lysosomes (Jimenez-Orgaz et al., 2018; Seaman et al., 2018).”

    From Acute inactivation of retromer and ESCPE-1 leads to time-resolved defects in endosomal cargo sorting (2020) · cites this paper as Jimenez-Orgaz et al., 2018

  • Besides its role in cargo retrieval and recycling within the endosomal pathway, retromer has emerged as a master regulator of RAB7 in nutrient sensing and signalling.

    “Thus, besides its role in cargo retrieval and recycling within the endosomal pathway (Steinberg et al., 2013), retromer has emerged as a master regulator of RAB7 in nutrient sensing and signalling (Jimenez-Orgaz et al., 2018; Curnock et al., 2019; Kvainickas et al., 2019).”

    From Acute inactivation of retromer and ESCPE-1 leads to time-resolved defects in endosomal cargo sorting (2020) · cites this paper as Jimenez-Orgaz et al., 2018

  • The knockout phenotype may in part reflect retromer's role as a master regulator of the activity state of endosomal RAB7 through binding to the RAB7 GAP TBC1D5.

    “In part, this phenotype may reflect the role of retromer as a master regulator (Jimenez-Orgaz et al., 2018) of the activity state of endosomal RAB7 through binding to the RAB7 GAP TBC1D5 (Seaman et al., 2009, 2018; Jimenez-Orgaz et al., 2018; Kvainickas et al., 2019).”

    From Acute inactivation of retromer and ESCPE-1 leads to time-resolved defects in endosomal cargo sorting (2020) · cites this paper as Jimenez-Orgaz et al., 2018

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Metadata

Authors
Jimenez‐Orgaz, A., Kvainickas, A., Nägele, H., Denner, J., Eimer, S., Dengjel, J., & Steinberg, F.
ORCID
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
2017-11-20
Volume
37
Issue
2
Pages
235-254
ISSN
  • 0261-4189
  • 1460-2075
DOI
10.15252/embj.201797128
PMC
PMC5770787
Cited by
211
References
3
Language
en
Licence
Funders
  • Deutsche Forschungsgemeinschaft (STE 2310/1‐1)
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A‐166482/1)

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