Regulated proteolysis of C andida albicans R as1 is involved in morphogenesis and quorum sensing regulation
Open accessAbstract
Summary: In C andida albicans , a fungal pathogen, the small G ‐protein R as1 regulates many important behaviors including white‐opaque switching, biofilm formation, and the induction and maintenance of hyphal growth. Like other R as proteins, R as1 is activated upon guanine triphosphate binding, and its activity is further modulated by post‐translational lipid modifications. Here, we report that the levels of membrane‐associated, full‐length Ras1 were higher in hyphae than in yeast, and that yeast contained a shorter, soluble Ras1 species that resulted from cleavage. Deletion of the putative cleavage site led to more rapid induction of hyphal growth and delayed hypha‐to‐yeast transitions. The cleaved R as1 species was less able to activate its effector, adenylate cyclase ( C yr1), unless tethered to the membrane by a heterologous membrane‐targeting domain. R as1 cleavage was repressed by cAMP ‐signalling, indicating the presence of a positive feedback loop in which Cyr1 and cAMP influence R as1. The C . albicans quorum sensing molecule farnesol, which inhibits Cyr1 and represses filamentation, caused an increase in the fraction of R as1 in the cleaved form, particularly in nascent yeast formed from hyphae. This newly recognized mode of R as regulation may control C . albicans R as1 activity in important ways.
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Pma1 was detected as a control protein.
“As a control protein Pma1 was detected as described previously [52].”
From Mitochondrial Activity and Cyr1 Are Key Regulators of Ras1 Activation of C. albicans Virulence Pathways (2015) · cites this paper as [52]
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Grahl, N., Demers, E. G., Lindsay, A. K., Harty, C. E., Willger, S. D., Piispanen, A. E., & Hogan, D. A. (2015) · PLOS Pathogens · doi:10.1371/journal.ppat.1005133 · Cited by 111 · see citing works
“Interestingly, the ras1Δ67 strain showed lower levels of GTP-Ras1 in control conditions compared to the ras1 N-term or wild type strain (S6 Fig) suggesting a possible GTP-binding inhibitory domain or function activated by Ras1 cleavage [52].”
BackgroundInfluentialSelf-citationGlobal Role of Cyclic AMP Signaling in pH-Dependent Responses in Candida albicans
Hollomon, J. M., Grahl, N., Willger, S. D., Koeppen, K., & Hogan, D. A. (2016) · mSphere · doi:10.1128/msphere.00283-16 · Cited by 22 · see citing works
Self-citation
- Authors
- Piispanen, A. E., Grahl, N., Hollomon, J. M., & Hogan, D. A.
- Affiliations
- Dartmouth College (US)
- Corresponding author
- Hogan, Deborah A.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2013-06-10
- Volume
- 89
- Issue
- 1
- Pages
- 166-178
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- PMC
- PMC3782256
- OpenAlex
- W2104253511
- Cited by
- 32
- References
- 56
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 4 · 2021: 2 · 2020: 2 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 4 · 2013: 3
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (T32GM008704)
- National Institute of Allergy and Infectious Diseases (T32AI007519)
- National Institute of Dental and Craniofacial Research (K22DE016542)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- Candida albicans, Ras1, regulated proteolysis, hyphal morphogenesis, white-opaque switching, quorum sensing, farnesol, cAMP signaling
- MeSH terms
- Candida albicans, DNA Mutational Analysis, Gene Expression Regulation, Fungal, Sequence Deletion, ras Proteins, Quorum Sensing, Proteolysis
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