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Published on: January 13, 2023
Candida albicans Pma1p Contributes to Growth, pH Homeostasis, and Hyphal Formation
Hallie S Rane1, Summer R Hayek1, Jillian E Frye2
1Department of Biochemistry and Molecular Biology, University of New Mexico Health Science Center, Albuquerque, NM, United States.
Abstract:
Candida albicans occupies diverse ecological niches within the host and must tolerate a wide range of environmental pH. The plasma membrane H+-ATPase Pma1p is the major regulator of cytosolic pH in fungi. Pma1p extrudes protons from the cytosol to maintain neutral-to-alkaline pH and is a potential drug target due to its essentiality and fungal specificity. We characterized mutants in which one allele of PMA1 has been deleted and the other truncated by 18-38 amino acids. Increasing C-terminal truncation caused corresponding decreases in plasma membrane ATPase-specific activity and cytosolic pH. Pma1p is regulated by glucose: glucose rapidly activates the ATPase, causing a sharp increase in cytosolic pH. Increasing Pma1p truncation severely impaired this glucose response. Pma1p truncation also altered cation responses, disrupted vacuolar morphology and pH, and reduced filamentation competence. Early studies of cytosolic pH and filamentation have described a rapid, transient alkalinization of the cytosol preceding germ tube formation; Pma1p has been proposed as a regulator of this process. We find Pma1p plays a role in the establishment of cell polarity, and distribution of Pma1p is non-homogenous in emerging hyphae. These findings suggest a role of PMA1 in cytosolic alkalinization and in the specialized form of polarized growth that is filamentation.
Insights
Candida albicans Pma1p, essential for fungal pH regulation, is crucial for glucose response and filamentation. Truncations impair its activity, affecting cytosolic pH and cell polarity.
Area of Science:
- Mycology
- Cell Biology
- Biochemistry
Background:
- Candida albicans inhabits diverse host niches, requiring pH tolerance.
- The plasma membrane H+-ATPase Pma1p is vital for fungal cytosolic pH homeostasis and is a potential antifungal drug target.
Purpose of the Study:
- To investigate the role of Pma1p in Candida albicans pH regulation, glucose response, and filamentation.
- To characterize the effects of Pma1p C-terminal truncations on its activity and cellular functions.
Main Methods:
- Characterization of Pma1p mutants with C-terminal truncations.
- Measurement of plasma membrane ATPase activity and cytosolic pH.
- Assessment of glucose-induced pH changes, cation responses, vacuolar morphology, and filamentation competence.
Main Results:
- Increasing Pma1p C-terminal truncation reduced ATPase activity, cytosolic pH, and the glucose-induced pH increase.
- Pma1p truncation impaired cation responses, altered vacuolar morphology and pH, and reduced filamentation.
- Pma1p plays a role in cell polarity establishment and its distribution is non-uniform in hyphae.
Conclusions:
- Pma1p is essential for regulating cytosolic pH and responding to glucose in Candida albicans.
- Pma1p truncation disrupts cellular homeostasis and filamentation, highlighting its importance in fungal growth and pathogenicity.
- Pma1p is implicated in establishing cell polarity and regulating the specialized growth form of filamentation.
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