Receptor-mediated endocytosis 8 (RME-8)/DNAJC13 is a novel positive modulator of autophagy and stabilizes cellular protein homeostasis

Publication type:
Journal article
Metadata:
Abstract
<jats:title>Abstract</jats:title><jats:p>The cellular protein homeostasis (proteostasis) network responds effectively to insults. In a functional screen in <jats:italic>C. elegans</jats:italic>, we recently identified the gene <jats:italic>receptor-mediated endocytosis 8</jats:italic> (<jats:italic>rme-8;</jats:italic> human ortholog: <jats:italic>DNAJC13</jats:italic>) as a component of the proteostasis network. Accumulation of aggregation-prone proteins, such as amyloid-β 42 (Aβ), α-synuclein, or mutant Cu/Zn-superoxide dismutase (SOD1), were aggravated upon the knockdown of <jats:italic>rme-8/DNAJC13</jats:italic> in <jats:italic>C. elegans</jats:italic> and in human cell lines, respectively. DNAJC13 is involved in endosomal protein trafficking and associated with the retromer and the WASH complex. As both complexes have been linked to autophagy, we investigated the role of DNAJC13 in this degradative pathway. In knockdown and overexpression experiments, DNAJC13 acts as a positive modulator of autophagy. In contrast, the overexpression of the Parkinson’s disease-associated mutant DNAJC13(N855S) did not enhance autophagy. Reduced DNAJC13 levels affected ATG9A localization at and its transport from the recycling endosome. As a consequence, ATG9A co-localization at LC3B-positive puncta under steady-state and autophagy-induced conditions is impaired. These data demonstrate a novel function of RME-8/DNAJC13 in cellular homeostasis by modulating ATG9A trafficking and autophagy.</jats:p>
Autoren
  • Anna S Besemer
  • Joanna Maus
  • Mirjam DA Ax
  • Anna Stein
  • Stella Vo
  • Christian Freese
  • Karsten Nalbach
  • Christian von Hilchen
  • Ines F Pfalzgraf
  • Ingrid Koziollek-Drechsler
  • Beate Silva
  • Heike Huesmann
  • Fatima Boukhallouk
  • Luise Florin
  • Andreas Kern
  • Christian Behl
  • Albrecht M Clement
DOI
10.1007/s00018-020-03521-y
eISSN
1420-9071
ISSN
1420-682X
Ausgabe der Veröffentlichung
2
Zeitschrift
Cellular and Molecular Life Sciences
Sprache
en
Online publication date
2020
Paginierung
645 - 660
Datum der Veröffentlichung
2021
Status
Published
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1007/s00018-020-03521-y
Datum der Datenerfassung
2021
Titel
Receptor-mediated endocytosis 8 (RME-8)/DNAJC13 is a novel positive modulator of autophagy and stabilizes cellular protein homeostasis
Ausgabe der Zeitschrift
78

Data source: Crossref

Other metadata sources:
Author's licence
CC-BY
Autoren
  • Anna S Besemer
  • Joanna Maus
  • Mirjam DA Ax
  • Anna Stein
  • Stella Vo
  • Christian Freese
  • Karsten Nalbach
  • Christian von Hilchen
  • Ines F Pfalzgraf
  • Ingrid Koziollek-Drechsler
  • Beate Silva
  • Heike Huesmann
  • Fatima Boukhallouk
  • Luise Florin
  • Andreas Kern
  • Christian Behl
  • Albrecht M Clement
Hosting institution
Universitätsbibliothek Mainz
Sammlungen
  • JGU-Publikationen
Resource version
Published version
DOI
10.1007/s00018-020-03521-y
File(s) embargoed
false
Open access
true
ISSN
1420-9071
Zeitschrift
Cellular and molecular life sciences
Schlüsselwörter
  • 540 Chemie
  • 540 Chemistry and allied sciences
  • 570 Biowissenschaften
  • 570 Life sciences
  • 610 Medizin
  • 610 Medical sciences
Sprache
eng
Open access status
Open Access
Paginierung
645 - 660
Datum der Veröffentlichung
2021
Public URL
https://openscience.ub.uni-mainz.de/handle/20.500.12030/5886
Herausgeber
Springer International Publishing AG
Herausgeber URL
https://doi.org/10.1007/s00018-020-03521-y
Datum der Datenerfassung
2021
Datum, an dem der Datensatz öffentlich gemacht wurde
2021
Zugang
Public
Titel
Receptor-mediated endocytosis 8 (RME-8)/DNAJC13 is a novel positive modulator of autophagy and stabilizes cellular protein homeostasis
Ausgabe der Zeitschrift
78

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besemer_anna_s.-receptor-media-20210503153859269.pdf

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