Removal of hypersignaling endosomes by simaphagy

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Migliano, Simona M.Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, Oslo, Norway. (author)

Removal of hypersignaling endosomes by simaphagy

Article/chapterEnglish2024

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Taylor & Francis,2024
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LIBRIS-ID:oai:DiVA.org:uu-530028
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-530028URI
https://doi.org/10.1080/15548627.2023.2267958DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Activated transmembrane receptors continue to signal following endocytosis and are only silenced upon ESCRT-mediated internalization of the receptors into intralumenal vesicles (ILVs) of the endosomes. Accordingly, endosomes with dysfunctional receptor internalization into ILVs can cause sustained receptor signaling which has been implicated in cancer progression. Here, we describe a surveillance mechanism that allows cells to detect and clear physically intact endosomes with aberrant receptor accumulation and elevated signaling. Proximity biotinylation and proteomics analyses of ESCRT-0 defective endosomes revealed a strong enrichment of the ubiquitin-binding macroautophagy/autophagy receptors SQSTM1 and NBR1, a phenotype that was confirmed in cell culture and fly tissue. Live cell microscopy demonstrated that loss of the ESCRT-0 subunit HGS/HRS or the ESCRT-I subunit VPS37 led to high levels of ubiquitinated and phosphorylated receptors on endosomes. This was accompanied by dynamic recruitment of NBR1 and SQSTM1 as well as proteins involved in autophagy initiation and autophagosome biogenesis. Light microscopy and electron tomography revealed that endosomes with intact limiting membrane, but aberrant receptor downregulation were engulfed by phagophores. Inhibition of autophagy caused increased intra- and intercellular signaling and directed cell migration. We conclude that dysfunctional endosomes are surveyed and cleared by an autophagic process, simaphagy, which serves as a failsafe mechanism in signal termination.

Subject headings and genre

NATURVETENSKAP Biologi Cellbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Cell Biology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
Autophagy
endosome
ESCRT
receptor degradation
signaling

Added entries (persons, corporate bodies, meetings, titles ...)

Schultz, Sebastian W.Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, Oslo, Norway. (author)
Wenzel, Eva M.Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, Oslo, Norway. (author)
Takáts, SzabolcsUniv Oslo, Fac Med, Ctr Canc Cell Reprogramming, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, Oslo, Norway.;Eotvos Lorand Univ, Dept Anat Cell & Dev Biol, Budapest, Hungary. (author)
Liu, DanUniv Oslo, Fac Med, Ctr Canc Cell Reprogramming, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, Oslo, Norway. (author)
Mørk, SiljeUniv Oslo, Fac Med, Ctr Canc Cell Reprogramming, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, Oslo, Norway. (author)
Tan, Kia WeeUppsala universitet,Institutionen för medicinsk cellbiologi,Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, Oslo, Norway; Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, Oslo, Norway(Swepub:uu)kiata789 (author)
Rusten, Tor ErikUniv Oslo, Fac Med, Ctr Canc Cell Reprogramming, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, Oslo, Norway. (author)
Raiborg, CamillaUniv Oslo, Fac Med, Ctr Canc Cell Reprogramming, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, Oslo, Norway. (author)
Stenmark, HaraldUniv Oslo, Fac Med, Ctr Canc Cell Reprogramming, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, Oslo, Norway. (author)
Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, Oslo, Norway.Univ Oslo, Fac Med, Ctr Canc Cell Reprogramming, Oslo, Norway.;Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, Oslo, Norway.;Eotvos Lorand Univ, Dept Anat Cell & Dev Biol, Budapest, Hungary. (creator_code:org_t)

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In:Autophagy: Taylor & Francis20:4, s. 769-7911554-86271554-8635

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NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Cell Biology

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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