期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 28, 页码 8644-8649出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1504259112
关键词
membrane traffic; filamentous growth; polarity; morphogenesis; lipid distribution
资金
- Centre National de la Recherche Scientifique
- Agence Nationale de la Recherche [ANR-13-BSV3-0006-01, ANR-11-LABX-0028-01]
- Association pour la Recherche sur le Cancer [20141201949]
- France-Berkeley Fund [2012-0056]
- European Union [PITN-GA-2013-607963]
- Platform of Resources in Imaging and Scientific Microscopy facility
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.
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