Authors:	Besemer, Anna S. Maus, Joanna Ax, Mirjam D. A. Stein, Anna Vo, Stella Freese, Christian Nalbach, Karsten Hilchen, Christian von Pfalzgraf, Ines F. Koziollek-Drechsler, Ingrid Silva, Beate Huesmann, Heike Boukhallouk, Fatima Florin, Luise Kern, Andreas Behl, Christian Clement, Albrecht M.
Title:	Receptor-mediated endocytosis 8 (RME-8)/DNAJC13 is a novel positive modulator of autophagy and stabilizes cellular protein homeostasis
Online publication date:	10-May-2021
Year of first publication:	2021
Language:	english
Abstract:	The cellular protein homeostasis (proteostasis) network responds effectively to insults. In a functional screen in C. elegans, we recently identified the gene receptor-mediated endocytosis 8 (rme-8; human ortholog: DNAJC13) 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 rme-8/DNAJC13 in C. elegans 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.
DDC:	540 Chemie 540 Chemistry and allied sciences 570 Biowissenschaften 570 Life sciences 610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-5877
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Cellular and molecular life sciences 78
Pages or article number:	645 660
Publisher:	Springer International Publishing AG
Publisher place:	Cham (ZG)
Issue date:	2021
ISSN:	1420-9071
Publisher URL:	https://doi.org/10.1007/s00018-020-03521-y
Publisher DOI:	10.1007/s00018-020-03521-y
Appears in collections:	JGU-Publikationen