Please use this identifier to cite or link to this item: doi:10.22028/D291-36807
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Title: The ER protein translocation channel subunit Sbh1 controls virulence of Cryptococcus neoformans
Author(s): Santiago-Tirado, Felipe H.
Hurtaux, Thomas
Geddes-McAlister, Jennifer
Nguyen, Duy
Helms, Volkhard
Doering, Tamara L.
Römisch, Karin
Language: English
Year of Publication: 2022
DDC notations: 570 Life sciences, biology
Publikation type: Other
Abstract: The fungal pathogen Cryptococcus neoformans is distinguished by a cell wall-anchored polysaccharide capsule that is critical for virulence. Biogenesis of both cell wall and capsule relies on the secretory pathway. Protein secretion begins with polypeptide translocation across the endoplasmic reticulum (ER) membrane through a highly conserved channel formed by three proteins: Sec61, Sbh1, and Sss1. Sbh1, the most divergent, contains multiple phosphorylation sites, which may allow it to regulate entry into the secretory pathway in a species- and protein-specific manner. Absence of SBH1 causes a cell-wall defect in both Saccharomyces cerevisiae and C. neoformans, although other phenotypes differ. Proteomic analysis revealed a set of secretory and transmembrane proteins whose expression under host-like conditions was upregulated in wild-type cryptococci, but not in Δsbh1 mutant cells. The Sbh1-dependent proteins show specific features of their ER targeting sequences that likely cause them to transit less efficiently into the secretory pathway. Many also act in cell-wall biogenesis, while several are known virulence factors; accordingly, the C. neoformans Δsbh1 mutant was avirulent in a mouse infection model. We conclude that, in the context of host-like conditions, Sbh1 controls the entry of virulence factors into the secretory pathway of Cryptococcus neoformans, and thereby regulates fungal pathogenicity.
DOI of the first publication: 10.1101/2022.06.01.494298
URL of the first publication: https://www.biorxiv.org/content/10.1101/2022.06.01.494298v1
Link to this record: urn:nbn:de:bsz:291--ds-368071
hdl:20.500.11880/33566
http://dx.doi.org/10.22028/D291-36807
Date of registration: 3-Aug-2022
Notes: Preprint
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Professorship: NT - Prof. Dr. Volkhard Helms
NT - Prof. Dr. Karin Römisch
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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