A central role for TOR signalling in a yeast model for juvenile CLN3 disease

Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. We study the role of btn1, the orthologue of a human gene that underlies a...

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Main Authors: Michael E. Bond, Rachel Brown, Charalampos Rallis, Jürg Bähler, Sara E. Mole
Format: Article
Language:English
Published: Shared Science Publishers OG 2015-11-01
Series:Microbial Cell
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Online Access:http://microbialcell.com/researcharticles/a-central-role-for-tor-signalling-in-a-yeast-model-for-juvenile-cln3-disease/
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author Michael E. Bond
Rachel Brown
Charalampos Rallis
Jürg Bähler
Sara E. Mole
author_facet Michael E. Bond
Rachel Brown
Charalampos Rallis
Jürg Bähler
Sara E. Mole
author_sort Michael E. Bond
collection DOAJ
description Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. We study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe. A global screen for genetic interactions with btn1 highlighted a conserved key signalling hub in which multiple components functionally relate to this conserved disease gene. This signalling hub includes two major mitogen-activated protein kinase (MAPK) cascades, and centers on the Tor kinase complexes TORC1 and TORC2. We confirmed that yeast cells modelling CLN3 disease exhibit features consistent with dysfunction in the TORC pathways, and showed that modulating TORC function leads to a comprehensive rescue of defects in this yeast disease model. The same pathways may be novel targets in the development of therapies for the NCLs and related diseases.
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spelling doaj-art-0e389bce9ca94d6ca39f46f268dae8012025-08-20T02:04:33ZengShared Science Publishers OGMicrobial Cell2311-26382015-11-0121246648010.15698/mic2015.12.241A central role for TOR signalling in a yeast model for juvenile CLN3 diseaseMichael E. Bond0Rachel Brown1Charalampos Rallis2Jürg Bähler3Sara E. Mole4MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK.Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK.MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. We study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe. A global screen for genetic interactions with btn1 highlighted a conserved key signalling hub in which multiple components functionally relate to this conserved disease gene. This signalling hub includes two major mitogen-activated protein kinase (MAPK) cascades, and centers on the Tor kinase complexes TORC1 and TORC2. We confirmed that yeast cells modelling CLN3 disease exhibit features consistent with dysfunction in the TORC pathways, and showed that modulating TORC function leads to a comprehensive rescue of defects in this yeast disease model. The same pathways may be novel targets in the development of therapies for the NCLs and related diseases.http://microbialcell.com/researcharticles/a-central-role-for-tor-signalling-in-a-yeast-model-for-juvenile-cln3-disease/Batten diseaseNCLCLN3btn1TorTORCS. pombeyeast
spellingShingle Michael E. Bond
Rachel Brown
Charalampos Rallis
Jürg Bähler
Sara E. Mole
A central role for TOR signalling in a yeast model for juvenile CLN3 disease
Microbial Cell
Batten disease
NCL
CLN3
btn1
Tor
TORC
S. pombe
yeast
title A central role for TOR signalling in a yeast model for juvenile CLN3 disease
title_full A central role for TOR signalling in a yeast model for juvenile CLN3 disease
title_fullStr A central role for TOR signalling in a yeast model for juvenile CLN3 disease
title_full_unstemmed A central role for TOR signalling in a yeast model for juvenile CLN3 disease
title_short A central role for TOR signalling in a yeast model for juvenile CLN3 disease
title_sort central role for tor signalling in a yeast model for juvenile cln3 disease
topic Batten disease
NCL
CLN3
btn1
Tor
TORC
S. pombe
yeast
url http://microbialcell.com/researcharticles/a-central-role-for-tor-signalling-in-a-yeast-model-for-juvenile-cln3-disease/
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