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Candida albicans SR-Like Protein Kinases Regulate Different Cellular Processes: Sky1 Is Involved in Control of Ion Homeostasis, While Sky2 Is Important for Dipeptide Utilization

Protein kinases play a crucial role in regulating cellular processes such as growth, proliferation, environmental adaptation and stress responses. Serine-arginine (SR) protein kinases are highly conserved in eukaryotes and regulate fundamental processes such as constitutive and alternative splicing,...

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Autores principales: Brandt, Philipp, Gerwien, Franziska, Wagner, Lysett, Krüger, Thomas, Ramírez-Zavala, Bernardo, Mirhakkak, Mohammad H., Schäuble, Sascha, Kniemeyer, Olaf, Panagiotou, Gianni, Brakhage, Axel A., Morschhäuser, Joachim, Vylkova, Slavena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121809/
https://www.ncbi.nlm.nih.gov/pubmed/35601106
http://dx.doi.org/10.3389/fcimb.2022.850531
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author Brandt, Philipp
Gerwien, Franziska
Wagner, Lysett
Krüger, Thomas
Ramírez-Zavala, Bernardo
Mirhakkak, Mohammad H.
Schäuble, Sascha
Kniemeyer, Olaf
Panagiotou, Gianni
Brakhage, Axel A.
Morschhäuser, Joachim
Vylkova, Slavena
author_facet Brandt, Philipp
Gerwien, Franziska
Wagner, Lysett
Krüger, Thomas
Ramírez-Zavala, Bernardo
Mirhakkak, Mohammad H.
Schäuble, Sascha
Kniemeyer, Olaf
Panagiotou, Gianni
Brakhage, Axel A.
Morschhäuser, Joachim
Vylkova, Slavena
author_sort Brandt, Philipp
collection PubMed
description Protein kinases play a crucial role in regulating cellular processes such as growth, proliferation, environmental adaptation and stress responses. Serine-arginine (SR) protein kinases are highly conserved in eukaryotes and regulate fundamental processes such as constitutive and alternative splicing, mRNA processing and ion homeostasis. The Candida albicans genome encodes two (Sky1, Sky2) and the Candida glabrata genome has one homolog (Sky1) of the human SR protein kinase 1, but their functions have not yet been investigated. We used deletion strains of the corresponding genes in both fungi to study their cellular functions. C. glabrata and C. albicans strains lacking SKY1 exhibited higher resistance to osmotic stress and toxic polyamine concentrations, similar to Saccharomyces cerevisiae sky1Δ mutants. Deletion of SKY2 in C. albicans resulted in impaired utilization of various dipeptides as the sole nitrogen source. Subsequent phosphoproteomic analysis identified the di- and tripeptide transporter Ptr22 as a potential Sky2 substrate. Sky2 seems to be involved in Ptr22 regulation since overexpression of PTR22 in the sky2Δ mutant restored the ability to grow on dipeptides and made the cells more susceptible to the dipeptide antifungals Polyoxin D and Nikkomycin Z. Altogether, our results demonstrate that C. albicans and C. glabrata Sky1 protein kinases are functionally similar to Sky1 in S. cerevisiae, whereas C. albicans Sky2, a unique kinase of the CTG clade, likely regulates dipeptide uptake via Ptr22.
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spelling pubmed-91218092022-05-21 Candida albicans SR-Like Protein Kinases Regulate Different Cellular Processes: Sky1 Is Involved in Control of Ion Homeostasis, While Sky2 Is Important for Dipeptide Utilization Brandt, Philipp Gerwien, Franziska Wagner, Lysett Krüger, Thomas Ramírez-Zavala, Bernardo Mirhakkak, Mohammad H. Schäuble, Sascha Kniemeyer, Olaf Panagiotou, Gianni Brakhage, Axel A. Morschhäuser, Joachim Vylkova, Slavena Front Cell Infect Microbiol Cellular and Infection Microbiology Protein kinases play a crucial role in regulating cellular processes such as growth, proliferation, environmental adaptation and stress responses. Serine-arginine (SR) protein kinases are highly conserved in eukaryotes and regulate fundamental processes such as constitutive and alternative splicing, mRNA processing and ion homeostasis. The Candida albicans genome encodes two (Sky1, Sky2) and the Candida glabrata genome has one homolog (Sky1) of the human SR protein kinase 1, but their functions have not yet been investigated. We used deletion strains of the corresponding genes in both fungi to study their cellular functions. C. glabrata and C. albicans strains lacking SKY1 exhibited higher resistance to osmotic stress and toxic polyamine concentrations, similar to Saccharomyces cerevisiae sky1Δ mutants. Deletion of SKY2 in C. albicans resulted in impaired utilization of various dipeptides as the sole nitrogen source. Subsequent phosphoproteomic analysis identified the di- and tripeptide transporter Ptr22 as a potential Sky2 substrate. Sky2 seems to be involved in Ptr22 regulation since overexpression of PTR22 in the sky2Δ mutant restored the ability to grow on dipeptides and made the cells more susceptible to the dipeptide antifungals Polyoxin D and Nikkomycin Z. Altogether, our results demonstrate that C. albicans and C. glabrata Sky1 protein kinases are functionally similar to Sky1 in S. cerevisiae, whereas C. albicans Sky2, a unique kinase of the CTG clade, likely regulates dipeptide uptake via Ptr22. Frontiers Media S.A. 2022-05-06 /pmc/articles/PMC9121809/ /pubmed/35601106 http://dx.doi.org/10.3389/fcimb.2022.850531 Text en Copyright © 2022 Brandt, Gerwien, Wagner, Krüger, Ramírez-Zavala, Mirhakkak, Schäuble, Kniemeyer, Panagiotou, Brakhage, Morschhäuser and Vylkova https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Brandt, Philipp
Gerwien, Franziska
Wagner, Lysett
Krüger, Thomas
Ramírez-Zavala, Bernardo
Mirhakkak, Mohammad H.
Schäuble, Sascha
Kniemeyer, Olaf
Panagiotou, Gianni
Brakhage, Axel A.
Morschhäuser, Joachim
Vylkova, Slavena
Candida albicans SR-Like Protein Kinases Regulate Different Cellular Processes: Sky1 Is Involved in Control of Ion Homeostasis, While Sky2 Is Important for Dipeptide Utilization
title Candida albicans SR-Like Protein Kinases Regulate Different Cellular Processes: Sky1 Is Involved in Control of Ion Homeostasis, While Sky2 Is Important for Dipeptide Utilization
title_full Candida albicans SR-Like Protein Kinases Regulate Different Cellular Processes: Sky1 Is Involved in Control of Ion Homeostasis, While Sky2 Is Important for Dipeptide Utilization
title_fullStr Candida albicans SR-Like Protein Kinases Regulate Different Cellular Processes: Sky1 Is Involved in Control of Ion Homeostasis, While Sky2 Is Important for Dipeptide Utilization
title_full_unstemmed Candida albicans SR-Like Protein Kinases Regulate Different Cellular Processes: Sky1 Is Involved in Control of Ion Homeostasis, While Sky2 Is Important for Dipeptide Utilization
title_short Candida albicans SR-Like Protein Kinases Regulate Different Cellular Processes: Sky1 Is Involved in Control of Ion Homeostasis, While Sky2 Is Important for Dipeptide Utilization
title_sort candida albicans sr-like protein kinases regulate different cellular processes: sky1 is involved in control of ion homeostasis, while sky2 is important for dipeptide utilization
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121809/
https://www.ncbi.nlm.nih.gov/pubmed/35601106
http://dx.doi.org/10.3389/fcimb.2022.850531
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