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Open AccessArticle

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

1
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland
2
Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Jacek Lenart had passed away.
Int. J. Mol. Sci. 2019, 20(20), 5067; https://doi.org/10.3390/ijms20205067
Received: 26 September 2019 / Revised: 11 October 2019 / Accepted: 11 October 2019 / Published: 12 October 2019
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. View Full-Text
Keywords: C. albicans; cell wall integrity; Cwh8p; dolichol; morphogenesis; Rer2p C. albicans; cell wall integrity; Cwh8p; dolichol; morphogenesis; Rer2p
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Janik, A.; Niewiadomska, M.; Perlińska-Lenart, U.; Lenart, J.; Kołakowski, D.; Skorupińska-Tudek, K.; Swiezewska, E.; Kruszewska, J.S.; Palamarczyk, G. Inhibition of Dephosphorylation of Dolichyl Diphosphate Alters the Synthesis of Dolichol and Hinders Protein N-Glycosylation and Morphological Transitions in Candida albicans. Int. J. Mol. Sci. 2019, 20, 5067.

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