Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD

Hexanucleotide repeat expansions in C9orf72 are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) (c9ALS/FTD). Unconventional translation of these repeats produces dipeptide repeat proteins (DPRs) that may cause neurodegeneration. We performed a modif...

Descripción completa

Detalles Bibliográficos
Autores principales: Boeynaems, Steven, Bogaert, Elke, Michiels, Emiel, Gijselinck, Ilse, Sieben, Anne, Jovičić, Ana, De Baets, Greet, Scheveneels, Wendy, Steyaert, Jolien, Cuijt, Ivy, Verstrepen, Kevin J., Callaerts, Patrick, Rousseau, Frederic, Schymkowitz, Joost, Cruts, Marc, Van Broeckhoven, Christine, Van Damme, Philip, Gitler, Aaron D., Robberecht, Wim, Van Den Bosch, Ludo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751451/
https://www.ncbi.nlm.nih.gov/pubmed/26869068
http://dx.doi.org/10.1038/srep20877
_version_ 1782415583786041344
author Boeynaems, Steven
Bogaert, Elke
Michiels, Emiel
Gijselinck, Ilse
Sieben, Anne
Jovičić, Ana
De Baets, Greet
Scheveneels, Wendy
Steyaert, Jolien
Cuijt, Ivy
Verstrepen, Kevin J.
Callaerts, Patrick
Rousseau, Frederic
Schymkowitz, Joost
Cruts, Marc
Van Broeckhoven, Christine
Van Damme, Philip
Gitler, Aaron D.
Robberecht, Wim
Van Den Bosch, Ludo
author_facet Boeynaems, Steven
Bogaert, Elke
Michiels, Emiel
Gijselinck, Ilse
Sieben, Anne
Jovičić, Ana
De Baets, Greet
Scheveneels, Wendy
Steyaert, Jolien
Cuijt, Ivy
Verstrepen, Kevin J.
Callaerts, Patrick
Rousseau, Frederic
Schymkowitz, Joost
Cruts, Marc
Van Broeckhoven, Christine
Van Damme, Philip
Gitler, Aaron D.
Robberecht, Wim
Van Den Bosch, Ludo
author_sort Boeynaems, Steven
collection PubMed
description Hexanucleotide repeat expansions in C9orf72 are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) (c9ALS/FTD). Unconventional translation of these repeats produces dipeptide repeat proteins (DPRs) that may cause neurodegeneration. We performed a modifier screen in Drosophila and discovered a critical role for importins and exportins, Ran-GTP cycle regulators, nuclear pore components, and arginine methylases in mediating DPR toxicity. These findings provide evidence for an important role for nucleocytoplasmic transport in the pathogenic mechanism of c9ALS/FTD.
format Online
Article
Text
id pubmed-4751451
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-47514512016-02-22 Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD Boeynaems, Steven Bogaert, Elke Michiels, Emiel Gijselinck, Ilse Sieben, Anne Jovičić, Ana De Baets, Greet Scheveneels, Wendy Steyaert, Jolien Cuijt, Ivy Verstrepen, Kevin J. Callaerts, Patrick Rousseau, Frederic Schymkowitz, Joost Cruts, Marc Van Broeckhoven, Christine Van Damme, Philip Gitler, Aaron D. Robberecht, Wim Van Den Bosch, Ludo Sci Rep Article Hexanucleotide repeat expansions in C9orf72 are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) (c9ALS/FTD). Unconventional translation of these repeats produces dipeptide repeat proteins (DPRs) that may cause neurodegeneration. We performed a modifier screen in Drosophila and discovered a critical role for importins and exportins, Ran-GTP cycle regulators, nuclear pore components, and arginine methylases in mediating DPR toxicity. These findings provide evidence for an important role for nucleocytoplasmic transport in the pathogenic mechanism of c9ALS/FTD. Nature Publishing Group 2016-02-12 /pmc/articles/PMC4751451/ /pubmed/26869068 http://dx.doi.org/10.1038/srep20877 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Boeynaems, Steven
Bogaert, Elke
Michiels, Emiel
Gijselinck, Ilse
Sieben, Anne
Jovičić, Ana
De Baets, Greet
Scheveneels, Wendy
Steyaert, Jolien
Cuijt, Ivy
Verstrepen, Kevin J.
Callaerts, Patrick
Rousseau, Frederic
Schymkowitz, Joost
Cruts, Marc
Van Broeckhoven, Christine
Van Damme, Philip
Gitler, Aaron D.
Robberecht, Wim
Van Den Bosch, Ludo
Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD
title Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD
title_full Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD
title_fullStr Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD
title_full_unstemmed Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD
title_short Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD
title_sort drosophila screen connects nuclear transport genes to dpr pathology in c9als/ftd
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751451/
https://www.ncbi.nlm.nih.gov/pubmed/26869068
http://dx.doi.org/10.1038/srep20877
work_keys_str_mv AT boeynaemssteven drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT bogaertelke drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT michielsemiel drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT gijselinckilse drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT siebenanne drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT jovicicana drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT debaetsgreet drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT scheveneelswendy drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT steyaertjolien drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT cuijtivy drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT verstrepenkevinj drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT callaertspatrick drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT rousseaufrederic drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT schymkowitzjoost drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT crutsmarc drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT vanbroeckhovenchristine drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT vandammephilip drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT gitleraarond drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT robberechtwim drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd
AT vandenboschludo drosophilascreenconnectsnucleartransportgenestodprpathologyinc9alsftd

Ejemplares similares