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Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants
Leishmania donovani is a trypanosomatidic parasite and causes the lethal kala-azar fever, a neglected tropical disease. The Trypanosomatida are devoid of transcriptional gene regulation and rely on gene copy number variations and translational control for their adaption to changing conditions. To su...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525241/ https://www.ncbi.nlm.nih.gov/pubmed/32994468 http://dx.doi.org/10.1038/s41598-020-72724-x |
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author | Kröber-Boncardo, Constanze Lorenzen, Stephan Brinker, Christine Clos, Joachim |
author_facet | Kröber-Boncardo, Constanze Lorenzen, Stephan Brinker, Christine Clos, Joachim |
author_sort | Kröber-Boncardo, Constanze |
collection | PubMed |
description | Leishmania donovani is a trypanosomatidic parasite and causes the lethal kala-azar fever, a neglected tropical disease. The Trypanosomatida are devoid of transcriptional gene regulation and rely on gene copy number variations and translational control for their adaption to changing conditions. To survive at mammalian tissue temperatures, L. donovani relies on the small heat shock protein HSP23, the loss of which renders the parasites stress sensitive and impairs their proliferation. Here, we analysed a spontaneous escape mutant with wild type-like in vitro growth. Further selection of this escape strains resulted in a complete reversion of the phenotype. Whole genome sequencing revealed a correlation between stress tolerance and the massive amplification of a six-gene cluster on chromosome 35, with further analysis showing over expression of the casein kinase 1.2 gene as responsible. In vitro phosphorylation experiments established both HSP23 and the related P23 co-chaperone as substrates and modulators of casein kinase 1.2, providing evidence for another crucial link between chaperones and signal transduction protein kinases in this early branching eukaryote. |
format | Online Article Text |
id | pubmed-7525241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75252412020-10-01 Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants Kröber-Boncardo, Constanze Lorenzen, Stephan Brinker, Christine Clos, Joachim Sci Rep Article Leishmania donovani is a trypanosomatidic parasite and causes the lethal kala-azar fever, a neglected tropical disease. The Trypanosomatida are devoid of transcriptional gene regulation and rely on gene copy number variations and translational control for their adaption to changing conditions. To survive at mammalian tissue temperatures, L. donovani relies on the small heat shock protein HSP23, the loss of which renders the parasites stress sensitive and impairs their proliferation. Here, we analysed a spontaneous escape mutant with wild type-like in vitro growth. Further selection of this escape strains resulted in a complete reversion of the phenotype. Whole genome sequencing revealed a correlation between stress tolerance and the massive amplification of a six-gene cluster on chromosome 35, with further analysis showing over expression of the casein kinase 1.2 gene as responsible. In vitro phosphorylation experiments established both HSP23 and the related P23 co-chaperone as substrates and modulators of casein kinase 1.2, providing evidence for another crucial link between chaperones and signal transduction protein kinases in this early branching eukaryote. Nature Publishing Group UK 2020-09-29 /pmc/articles/PMC7525241/ /pubmed/32994468 http://dx.doi.org/10.1038/s41598-020-72724-x Text en © The Author(s) 2020 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kröber-Boncardo, Constanze Lorenzen, Stephan Brinker, Christine Clos, Joachim Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants |
title | Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants |
title_full | Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants |
title_fullStr | Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants |
title_full_unstemmed | Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants |
title_short | Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants |
title_sort | casein kinase 1.2 over expression restores stress resistance to leishmania donovani hsp23 null mutants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525241/ https://www.ncbi.nlm.nih.gov/pubmed/32994468 http://dx.doi.org/10.1038/s41598-020-72724-x |
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