CO<sub>2</sub> Signaling through the Ptc2-Ssn3 Axis Governs Sustained Hyphal Development of <named-content content-type="genus-species">Candida albicans</named-content> by Reducing Ume6 Phosphorylation and Degradation
ABSTRACT Candida albicans is the most common cause of invasive fungal infections in humans. Its ability to sense and adapt to changing carbon dioxide levels is crucial for its pathogenesis. Carbon dioxide promotes hyphal development. The hypha-specific transcription factor Ume6 is rapidly degraded i...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2019-02-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02320-18 |
| _version_ | 1818995548595683328 |
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| author | Yang Lu Chang Su Shatarupa Ray Yuncong Yuan Haoping Liu |
| author_facet | Yang Lu Chang Su Shatarupa Ray Yuncong Yuan Haoping Liu |
| author_sort | Yang Lu |
| collection | DOAJ |
| description | ABSTRACT Candida albicans is the most common cause of invasive fungal infections in humans. Its ability to sense and adapt to changing carbon dioxide levels is crucial for its pathogenesis. Carbon dioxide promotes hyphal development. The hypha-specific transcription factor Ume6 is rapidly degraded in air, but is stable under physiological CO2 and hypoxia to sustain hyphal elongation. Here, we show that Ume6 stability is regulated by two parallel E3 ubiquitin ligases, SCFGrr1 and Ubr1, in response to CO2 and O2, respectively. To uncover the CO2 signaling pathway that regulates Ume6 stability, we performed genetic screens for mutants unable to respond to CO2 for sustained filamentation. We find that the type 2C protein phosphatase Ptc2 is specifically required for CO2-induced stabilization of Ume6 and hyphal elongation. In contrast, the cyclin-dependent kinase Ssn3 is found to be required for Ume6 phosphorylation and degradation in atmospheric CO2. Furthermore, we find that Ssn3 is dephosphorylated in 5% CO2 in a Ptc2-dependent manner, whereas deletion of PTC2 has no effect on Ssn3 phosphorylation in air. Our study uncovers the Ptc2-Ssn3 axis as a new CO2 signaling pathway that controls hyphal elongation by regulating Ume6 stability in C. albicans. IMPORTANCE The capacity to sense and adapt to changing carbon dioxide levels is crucial for all organisms. In fungi, CO2 is a key determinant involved in fundamental biological processes, including growth, morphology, and virulence. In the pathogenic fungus Candida albicans, high CO2 is directly sensed by adenylyl cyclase to promote hyphal growth. However, little is known about the mechanism by which hyphal development is maintained in response to physiological levels of CO2. Here we report that a signal transduction system mediated by a phosphatase-kinase pair controls CO2-responsive Ume6 phosphorylation and stability that in turn dictate hyphal elongation. Our results unravel a new regulatory mechanism of CO2 signaling in fungi. |
| first_indexed | 2024-12-20T21:15:36Z |
| format | Article |
| id | doaj.art-df8a98c13a264c1b912927001b3d761a |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-20T21:15:36Z |
| publishDate | 2019-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-df8a98c13a264c1b912927001b3d761a2022-12-21T19:26:26ZengAmerican Society for MicrobiologymBio2150-75112019-02-0110110.1128/mBio.02320-18CO<sub>2</sub> Signaling through the Ptc2-Ssn3 Axis Governs Sustained Hyphal Development of <named-content content-type="genus-species">Candida albicans</named-content> by Reducing Ume6 Phosphorylation and DegradationYang Lu0Chang Su1Shatarupa Ray2Yuncong Yuan3Haoping Liu4Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, ChinaHubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, ChinaDepartment of Biological Chemistry, School of Medicine, University of California, Irvine, California, USAHubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, ChinaDepartment of Biological Chemistry, School of Medicine, University of California, Irvine, California, USAABSTRACT Candida albicans is the most common cause of invasive fungal infections in humans. Its ability to sense and adapt to changing carbon dioxide levels is crucial for its pathogenesis. Carbon dioxide promotes hyphal development. The hypha-specific transcription factor Ume6 is rapidly degraded in air, but is stable under physiological CO2 and hypoxia to sustain hyphal elongation. Here, we show that Ume6 stability is regulated by two parallel E3 ubiquitin ligases, SCFGrr1 and Ubr1, in response to CO2 and O2, respectively. To uncover the CO2 signaling pathway that regulates Ume6 stability, we performed genetic screens for mutants unable to respond to CO2 for sustained filamentation. We find that the type 2C protein phosphatase Ptc2 is specifically required for CO2-induced stabilization of Ume6 and hyphal elongation. In contrast, the cyclin-dependent kinase Ssn3 is found to be required for Ume6 phosphorylation and degradation in atmospheric CO2. Furthermore, we find that Ssn3 is dephosphorylated in 5% CO2 in a Ptc2-dependent manner, whereas deletion of PTC2 has no effect on Ssn3 phosphorylation in air. Our study uncovers the Ptc2-Ssn3 axis as a new CO2 signaling pathway that controls hyphal elongation by regulating Ume6 stability in C. albicans. IMPORTANCE The capacity to sense and adapt to changing carbon dioxide levels is crucial for all organisms. In fungi, CO2 is a key determinant involved in fundamental biological processes, including growth, morphology, and virulence. In the pathogenic fungus Candida albicans, high CO2 is directly sensed by adenylyl cyclase to promote hyphal growth. However, little is known about the mechanism by which hyphal development is maintained in response to physiological levels of CO2. Here we report that a signal transduction system mediated by a phosphatase-kinase pair controls CO2-responsive Ume6 phosphorylation and stability that in turn dictate hyphal elongation. Our results unravel a new regulatory mechanism of CO2 signaling in fungi.https://journals.asm.org/doi/10.1128/mBio.02320-18Candida albicansSsn3/Cdk8Ume6carbon dioxide signalinghyphal development |
| spellingShingle | Yang Lu Chang Su Shatarupa Ray Yuncong Yuan Haoping Liu CO<sub>2</sub> Signaling through the Ptc2-Ssn3 Axis Governs Sustained Hyphal Development of <named-content content-type="genus-species">Candida albicans</named-content> by Reducing Ume6 Phosphorylation and Degradation mBio Candida albicans Ssn3/Cdk8 Ume6 carbon dioxide signaling hyphal development |
| title | CO<sub>2</sub> Signaling through the Ptc2-Ssn3 Axis Governs Sustained Hyphal Development of <named-content content-type="genus-species">Candida albicans</named-content> by Reducing Ume6 Phosphorylation and Degradation |
| title_full | CO<sub>2</sub> Signaling through the Ptc2-Ssn3 Axis Governs Sustained Hyphal Development of <named-content content-type="genus-species">Candida albicans</named-content> by Reducing Ume6 Phosphorylation and Degradation |
| title_fullStr | CO<sub>2</sub> Signaling through the Ptc2-Ssn3 Axis Governs Sustained Hyphal Development of <named-content content-type="genus-species">Candida albicans</named-content> by Reducing Ume6 Phosphorylation and Degradation |
| title_full_unstemmed | CO<sub>2</sub> Signaling through the Ptc2-Ssn3 Axis Governs Sustained Hyphal Development of <named-content content-type="genus-species">Candida albicans</named-content> by Reducing Ume6 Phosphorylation and Degradation |
| title_short | CO<sub>2</sub> Signaling through the Ptc2-Ssn3 Axis Governs Sustained Hyphal Development of <named-content content-type="genus-species">Candida albicans</named-content> by Reducing Ume6 Phosphorylation and Degradation |
| title_sort | co sub 2 sub signaling through the ptc2 ssn3 axis governs sustained hyphal development of named content content type genus species candida albicans named content by reducing ume6 phosphorylation and degradation |
| topic | Candida albicans Ssn3/Cdk8 Ume6 carbon dioxide signaling hyphal development |
| url | https://journals.asm.org/doi/10.1128/mBio.02320-18 |
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