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Inhibition of Dephosphorylation of Dolichyl Diphosphate Alters the Synthesis of Dolichol and Hinders Protein N-Glycosylation and Morphological Transitions in Candida albicans

The essential role of dolichyl phosphate (DolP) as a carbohydrate carrier during protein N-glycosylation is well established. The cellular pool of DolP is derived from de novo synthesis in the dolichol branch of the mevalonate pathway and from recycling of DolPP after each cycle of N-glycosylation,...

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Autores principales: Janik, Anna, Niewiadomska, Monika, Perlińska-Lenart, Urszula, Lenart, Jacek, Kołakowski, Damian, Skorupińska-Tudek, Karolina, Swiezewska, Ewa, Kruszewska, Joanna S., Palamarczyk, Grażyna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829516/
https://www.ncbi.nlm.nih.gov/pubmed/31614738
http://dx.doi.org/10.3390/ijms20205067
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author Janik, Anna
Niewiadomska, Monika
Perlińska-Lenart, Urszula
Lenart, Jacek
Kołakowski, Damian
Skorupińska-Tudek, Karolina
Swiezewska, Ewa
Kruszewska, Joanna S.
Palamarczyk, Grażyna
author_facet Janik, Anna
Niewiadomska, Monika
Perlińska-Lenart, Urszula
Lenart, Jacek
Kołakowski, Damian
Skorupińska-Tudek, Karolina
Swiezewska, Ewa
Kruszewska, Joanna S.
Palamarczyk, Grażyna
author_sort Janik, Anna
collection PubMed
description The essential role of dolichyl phosphate (DolP) as a carbohydrate carrier during protein N-glycosylation is well established. The cellular pool of DolP is derived from de novo synthesis in the dolichol branch of the mevalonate pathway and from recycling of DolPP after each cycle of N-glycosylation, when the oligosaccharide is transferred from the lipid carrier to the protein and DolPP is released and then dephosphorylated. In Saccharomyces cerevisiae, the dephosphorylation of DolPP is known to be catalyzed by the Cwh8p protein. To establish the role of the Cwh8p orthologue in another distantly related yeast species, Candida albicans, we studied its mutant devoid of the CaCWH8 gene. A double Cacwh8∆/Cacwh8∆ strain was constructed by the URA-blaster method. As in S. cerevisiae, the mutant was impaired in DolPP recycling. This defect, however, was accompanied by an elevation of cis-prenyltransferase activity and higher de novo production of dolichols. Despite these compensatory changes, protein glycosylation, cell wall integrity, filamentous growth, and biofilm formation were impaired in the mutant. These results suggest that the defects are not due to the lack of DolP for the protein N-glycosylation but rather that the activity of oligosacharyltransferase could be inhibited by the excess DolPP accumulating in the mutant.
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spelling pubmed-68295162019-11-18 Inhibition of Dephosphorylation of Dolichyl Diphosphate Alters the Synthesis of Dolichol and Hinders Protein N-Glycosylation and Morphological Transitions in Candida albicans Janik, Anna Niewiadomska, Monika Perlińska-Lenart, Urszula Lenart, Jacek Kołakowski, Damian Skorupińska-Tudek, Karolina Swiezewska, Ewa Kruszewska, Joanna S. Palamarczyk, Grażyna Int J Mol Sci Article The essential role of dolichyl phosphate (DolP) as a carbohydrate carrier during protein N-glycosylation is well established. The cellular pool of DolP is derived from de novo synthesis in the dolichol branch of the mevalonate pathway and from recycling of DolPP after each cycle of N-glycosylation, when the oligosaccharide is transferred from the lipid carrier to the protein and DolPP is released and then dephosphorylated. In Saccharomyces cerevisiae, the dephosphorylation of DolPP is known to be catalyzed by the Cwh8p protein. To establish the role of the Cwh8p orthologue in another distantly related yeast species, Candida albicans, we studied its mutant devoid of the CaCWH8 gene. A double Cacwh8∆/Cacwh8∆ strain was constructed by the URA-blaster method. As in S. cerevisiae, the mutant was impaired in DolPP recycling. This defect, however, was accompanied by an elevation of cis-prenyltransferase activity and higher de novo production of dolichols. Despite these compensatory changes, protein glycosylation, cell wall integrity, filamentous growth, and biofilm formation were impaired in the mutant. These results suggest that the defects are not due to the lack of DolP for the protein N-glycosylation but rather that the activity of oligosacharyltransferase could be inhibited by the excess DolPP accumulating in the mutant. MDPI 2019-10-12 /pmc/articles/PMC6829516/ /pubmed/31614738 http://dx.doi.org/10.3390/ijms20205067 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Janik, Anna
Niewiadomska, Monika
Perlińska-Lenart, Urszula
Lenart, Jacek
Kołakowski, Damian
Skorupińska-Tudek, Karolina
Swiezewska, Ewa
Kruszewska, Joanna S.
Palamarczyk, Grażyna
Inhibition of Dephosphorylation of Dolichyl Diphosphate Alters the Synthesis of Dolichol and Hinders Protein N-Glycosylation and Morphological Transitions in Candida albicans
title Inhibition of Dephosphorylation of Dolichyl Diphosphate Alters the Synthesis of Dolichol and Hinders Protein N-Glycosylation and Morphological Transitions in Candida albicans
title_full Inhibition of Dephosphorylation of Dolichyl Diphosphate Alters the Synthesis of Dolichol and Hinders Protein N-Glycosylation and Morphological Transitions in Candida albicans
title_fullStr Inhibition of Dephosphorylation of Dolichyl Diphosphate Alters the Synthesis of Dolichol and Hinders Protein N-Glycosylation and Morphological Transitions in Candida albicans
title_full_unstemmed Inhibition of Dephosphorylation of Dolichyl Diphosphate Alters the Synthesis of Dolichol and Hinders Protein N-Glycosylation and Morphological Transitions in Candida albicans
title_short Inhibition of Dephosphorylation of Dolichyl Diphosphate Alters the Synthesis of Dolichol and Hinders Protein N-Glycosylation and Morphological Transitions in Candida albicans
title_sort inhibition of dephosphorylation of dolichyl diphosphate alters the synthesis of dolichol and hinders protein n-glycosylation and morphological transitions in candida albicans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829516/
https://www.ncbi.nlm.nih.gov/pubmed/31614738
http://dx.doi.org/10.3390/ijms20205067
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