A DNM2 Centronuclear Myopathy Mutation Reveals a Link between Recycling Endosome Scission and Autophagy.
DNM2
ITSN1
RAB11
autophagosome
autophagy
centronuclear myopathy
phagophore
recycling endosome
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
20 04 2020
20 04 2020
Historique:
received:
21
08
2019
revised:
24
01
2020
accepted:
23
03
2020
entrez:
22
4
2020
pubmed:
22
4
2020
medline:
15
12
2020
Statut:
ppublish
Résumé
Autophagy involves engulfment of cytoplasmic contents by double-membraned autophagosomes, which ultimately fuse with lysosomes to enable degradation of their substrates. We recently proposed that the tubular-vesicular recycling endosome membranes were a core platform on which the critical early events of autophagosome formation occurred, including LC3-membrane conjugation to autophagic precursors. Here, we report that the release of autophagosome precursors from recycling endosomes is mediated by DNM2-dependent scission of these tubules. This process is regulated by DNM2 binding to LC3 and is increased by autophagy-inducing stimuli. This scission is defective in cells expressing a centronuclear-myopathy-causing DNM2 mutant. This mutant has an unusual mechanism as it depletes normal-functioning DNM2 from autophagosome formation sites on recycling endosomes by causing increased binding to an alternative plasma membrane partner, ITSN1. This "scission" step is, thus, critical for autophagosome formation, is defective in a human disease, and influences the way we consider how autophagosomes are formed.
Identifiants
pubmed: 32315611
pii: S1534-5807(20)30230-6
doi: 10.1016/j.devcel.2020.03.018
pii:
doi:
Substances chimiques
Adaptor Proteins, Vesicular Transport
0
ITSN1 protein, human
0
MAP1LC3A protein, human
0
Microtubule-Associated Proteins
0
DNM2 protein, human
EC 3.6.5.5
Dynamin II
EC 3.6.5.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
154-168.e6Subventions
Organisme : Medical Research Council
ID : MC_U105161083
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T012412/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : UKDRI-2002
Pays : United Kingdom
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests F.M.M. is employed by Eli Lilly, and D.C.R. is CSO of Aladdin Healthcare Technologies.