Dynamin-2 Regulates Postsynaptic Cytoskeleton Organization and Neuromuscular Junction Development.
NMJ morphogenesis
actin-bundling protein
centronuclear myopathy
phosphorylation of Dyn2(Y597)
podosome turnover
postsynaptic actin
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
27 10 2020
27 10 2020
Historique:
received:
03
03
2020
revised:
23
09
2020
accepted:
05
10
2020
entrez:
28
10
2020
pubmed:
29
10
2020
medline:
20
11
2021
Statut:
ppublish
Résumé
Neuromuscular junctions (NMJs) govern efficient neuronal communication with muscle cells, relying on proper architecture of specialized postsynaptic compartments. However, the intrinsic mechanism in muscle cells contributing to NMJ development remains unclear. In this study, we reveal that dynamin-2 (Dyn2) is involved in postsynaptic development of NMJs. Mutations of Dyn2 have been linked to human muscular disorder and centronuclear myopathy (CNM), as well as featured with muscle atrophy and defective NMJs, yet the function of Dyn2 at the postsynaptic membrane is largely unknown. We demonstrate that Dyn2 is enriched at the postsynaptic membrane and regulates NMJ development via actin remodeling. Dyn2 functions as an actin-bundling GTPase to regulate podosome turnover and cytoskeletal organization of the postsynaptic apparatus, and CNM-Dyn2 mutations display abnormal actin remodeling and electrophysiological activity of fly NMJs. Altogether, Dyn2 primarily regulates actin cytoskeleton remodeling and NMJ morphogenesis at the postsynaptic membrane, which is distinct from its endocytosis regulatory role at the presynaptic membrane.
Identifiants
pubmed: 33113375
pii: S2211-1247(20)31299-7
doi: 10.1016/j.celrep.2020.108310
pii:
doi:
Substances chimiques
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
108310Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.