The Cryptococcus neoformans alkaline response pathway: identification of a novel rim pathway activator
| العنوان: | The Cryptococcus neoformans alkaline response pathway: identification of a novel rim pathway activator |
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| المؤلفون: | Naureen Huda, J. Andrew Alspaugh, Shannon K. Esher, Teresa R. O’Meara, Kyla S. Ost |
| المصدر: | PLoS Genetics, Vol 11, Iss 4, p e1005159 (2015) PLoS Genetics |
| بيانات النشر: | Public Library of Science (PLoS), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Transcriptional Activation, Cancer Research, lcsh:QH426-470, Saccharomyces cerevisiae, Alkalies, Fungal Proteins, 03 medical and health sciences, Aspergillus nidulans, Cysteine Proteases, Genetics, Molecular Biology, Gene, Transcription factor, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Cryptococcus neoformans, 0303 health sciences, biology, Endosomal Sorting Complexes Required for Transport, 030306 microbiology, Activator (genetics), biology.organism_classification, ESCRT complex, lcsh:Genetics, Biochemistry, Membrane protein, Signal Transduction, Transcription Factors, Research Article |
| الوصف: | The Rim101/PacC transcription factor acts in a fungal-specific signaling pathway responsible for sensing extracellular pH signals. First characterized in ascomycete fungi such as Aspergillus nidulans and Saccharomyces cerevisiae, the Rim/Pal pathway maintains conserved features among very distantly related fungi, where it coordinates cellular adaptation to alkaline pH signals and micronutrient deprivation. However, it also directs species-specific functions in fungal pathogens such as Cryptococcus neoformans, where it controls surface capsule expression. Moreover, disruption of the Rim pathway central transcription factor, Rim101, results in a strain that causes a hyper-inflammatory response in animal infection models. Using targeted gene deletions, we demonstrate that several genes encoding components of the classical Rim/Pal pathway are present in the C. neoformans genome. Many of these genes are in fact required for Rim101 activation, including members of the ESCRT complex (Vps23 and Snf7), ESCRT-interacting proteins (Rim20 and Rim23), and the predicted Rim13 protease. We demonstrate that in neutral/alkaline pH, Rim23 is recruited to punctate regions on the plasma membrane. This change in Rim23 localization requires upstream ESCRT complex components but does not require other Rim101 proteolysis components, such as Rim20 or Rim13. Using a forward genetics screen, we identified the RRA1 gene encoding a novel membrane protein that is also required for Rim101 protein activation and, like the ESCRT complex, is functionally upstream of Rim23-membrane localization. Homologs of RRA1 are present in other Cryptococcus species as well as other basidiomycetes, but closely related genes are not present in ascomycetes. These findings suggest that major branches of the fungal Kingdom developed different mechanisms to sense and respond to very elemental extracellular signals such as changing pH levels. Author Summary Microorganisms that cause human disease use various cues to determine when they encounter a host. One of these signals is the slightly alkaline pH of human tissues. We have defined components of a pH-responsive signaling pathway in the human fungal pathogen Cryptococcus neoformans. This particular signaling pathway is specific for fungi and important for the virulence of several plant and animal pathogens. We have identified a previously unknown protein that activates this pH-sensing pathway. This protein and its downstream signaling pathway play a major role in the interaction of this fungal pathogen and the host immune system. |
| اللغة: | English |
| تدمد: | 1553-7404 1553-7390 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::086eeea13331aa7b3bdfe30c97bccfd7 http://europepmc.org/articles/PMC4393102?pdf=render |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....086eeea13331aa7b3bdfe30c97bccfd7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537404 15537390 |
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