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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

Janik, Anna and Niewiadomska, Monika and Perlinska-Lenart, Urszula and Lenart, Jacek and Kolakowski, Damian and Skorupinska-Tudek, Karolina and Swiezewska, Ewa and Kruszewska, Joanna S. and Palamarczyk, Grazyna (2019) Inhibition of Dephosphorylation of Dolichyl Diphosphate Alters the Synthesis of Dolichol and Hinders Protein N-Glycosylation and Morphological Transitions in Candida albicans. International Journal of Molecular Sciences, 20 (5067). pp. 1-19.

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Abstract

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.

Item Type:Article
Subjects:Q Science > Q Science (General)
Divisions:Laboratory of Fungal Glycobiology
ID Code:1762
Deposited By: prof dr hab Joanna S. Kruszewska
Deposited On:15 Oct 2019 12:44
Last Modified:15 Oct 2019 12:44

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