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

Bond, Michael and Brown, Rachel and Rallis, Charalampos and Bahler, Jurg and Mole, Sara (2015) 'A central role for TOR signalling in a yeast model for juvenile CLN3 disease.' Microbial Cell, 2 (12). 466 - 480. ISSN 2311-2638

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Abstract

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.

Item Type: Article
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Elements
Date Deposited: 18 Jun 2021 15:27
Last Modified: 18 Jun 2021 16:15
URI: http://repository.essex.ac.uk/id/eprint/26697

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