ATM phosphorylation of the actin-binding protein drebrin controls oxidation stress-resistance in mammalian neurons and C. elegans

  • Drebrin (DBN) regulates cytoskeletal functions during neuronal development, and is thought to contribute to structural and functional synaptic changes associated with aging and Alzheimer’s disease. Here we show that DBN coordinates stress signalling with cytoskeletal dynamics, via a mechanism involving kinase ataxia-telangiectasia mutated (ATM). An excess of reactive oxygen species (ROS) stimulates ATM-dependent phosphorylation of DBN at serine-647, which enhances protein stability and accounts for improved stress resilience in dendritic spines. We generated a humanized DBN Caenorhabditis elegans model and show that a phospho-DBN mutant disrupts the protective ATM effect on lifespan under sustained oxidative stress. Our data indicate a master regulatory function of ATM-DBN in integrating cytosolic stress-induced signalling with the dynamics of actin remodelling to provide protection from synapse dysfunction and ROS-triggered reduced lifespan. They further suggest that DBN protein abundance governs actin filament stability to contribute to the consequences of oxidative stress in physiological and pathological conditions.
Metadaten
Author:Patricia Kreis, Christian Gallrein, Eugenia Rojas Puente, Till G. A. Mack, Cristina Kroon, Viktor Dinkel, Claudia Willmes, Kai Murk, Susanne tom-Dieck, Erin Schuman, Janine Kirstein, Britta Eickholt
URN:urn:nbn:de:hebis:30:3-502463
DOI:https://doi.org/10.1038/s41467-019-08420-w
ISSN:2041-1723
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30700723
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/01/30
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/05/13
Tag:Actin; Cellular neuroscience
Volume:10
Issue:1, Art. 486
Page Number:13
First Page:1
Last Page:13
Note:
Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
HeBIS-PPN:45096535X
Institutes:Biowissenschaften / Biowissenschaften
Angeschlossene und kooperierende Institutionen / MPI für Hirnforschung
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 59 Tiere (Zoologie) / 590 Tiere (Zoologie)
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0