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Published on: October 23, 2016
Phosphatidylinositol-4-phosphate-dependent membrane traffic is critical for fungal filamentous growth
Vikram Ghugtyal1, Rocio Garcia-Rodas1, Agnese Seminara2
1Université de Nice-Sophia Antipolis, Institute of Biology Valrose, Parc Valrose, 06108 Nice Cedex 2, France; CNRS Institute of Biology Valrose, UMR7277, Parc Valrose, 06108 Nice Cedex 2, France; INSERM Institute of Biology Valrose, UMR1091, Parc Valrose, 06108 Nice Cedex 2, France;
Abstract:
The phospholipid phosphatidylinositol-4-phosphate [PI(4)P], generated at the Golgi and plasma membrane, has been implicated in many processes, including membrane traffic, yet its role in cell morphology changes, such as the budding to filamentous growth transition, is unknown. We show that Golgi PI(4)P is required for such a transition in the human pathogenic fungus Candida albicans. Quantitative analyses of membrane traffic revealed that PI(4)P is required for late Golgi and secretory vesicle dynamics and targeting and, as a result, is important for the distribution of a multidrug transporter and hence sensitivity to antifungal drugs. We also observed that plasma membrane PI(4)P, which we show is functionally distinct from Golgi PI(4)P, forms a steep gradient concomitant with filamentous growth, despite uniform plasma membrane PI-4-kinase distribution. Mathematical modeling indicates that local PI(4)P generation and hydrolysis by phosphatases are crucial for this gradient. We conclude that PI(4)P-regulated membrane dynamics are critical for morphology changes.
Insights
Phosphatidylinositol-4-phosphate (PI(4)P) is crucial for the pathogenic fungus Candida albicans to transition between budding and filamentous growth. This phospholipid regulates membrane traffic, affecting antifungal drug sensitivity.
Area of Science:
- Cell Biology
- Mycology
- Biochemistry
Background:
- Phosphatidylinositol-4-phosphate (PI(4)P) is a key phospholipid involved in membrane traffic.
- Its role in fungal cell morphology transitions, specifically the budding to filamentous growth switch, remains largely unexplored.
Purpose of the Study:
- To investigate the role of PI(4)P in the morphological transition of Candida albicans.
- To elucidate the function of Golgi and plasma membrane PI(4)P in this process.
Main Methods:
- Quantitative analysis of membrane traffic dynamics.
- Mathematical modeling of PI(4)P gradients.
- Functional studies in Candida albicans.
Main Results:
- Golgi PI(4)P is essential for the budding to filamentous growth transition in Candida albicans.
- PI(4)P regulates late Golgi and secretory vesicle dynamics and targeting.
- Plasma membrane PI(4)P forms a gradient during filamentous growth, distinct from Golgi PI(4)P's function.
- PI(4)P distribution impacts multidrug transporter localization and antifungal drug sensitivity.
Conclusions:
- PI(4)P-regulated membrane dynamics are critical for fungal morphology changes.
- Distinct roles of Golgi and plasma membrane PI(4)P highlight complex regulatory mechanisms.
- Targeting PI(4)P pathways could offer new strategies for antifungal drug development.
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