A Gβ protein and the TupA Co-Regulator Bind to Protein Kinase A Tpk2 to Act as Antagonistic Molecular Switches of Fungal Morphological Changes
| Autor: | Adrian R. Walmsley, Daliang Chen, João F. Menino, Thamarai K. Janganan, Fernando Rodrigues, Maria Inês Borges-Walmsley, Gongyou Chen |
|---|---|
| Přispěvatelé: | Universidade do Minho |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Saccharomyces cerevisiae Proteins
education Saccharomyces cerevisiae lcsh:Medicine Adenylate kinase Plasma protein binding Cell morphology 03 medical and health sciences Pseudohyphal growth Morphogenesis Kinase activity lcsh:Science Protein kinase A skin and connective tissue diseases health care economics and organizations 030304 developmental biology Paracoccidioides brasiliensis 0303 health sciences Multidisciplinary Science & Technology biology 030306 microbiology lcsh:R Genetic Complementation Test Paracoccidioides biology.organism_classification Cyclic AMP-Dependent Protein Kinases Cell biology lcsh:Q sense organs Research Article Protein Binding |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 9, p e0136866 (2015) PLoS ONE, 2015, Vol.10(9), pp.e0136866 [Peer Reviewed Journal] Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| ISSN: | 1932-6203 |
| Popis: | A Gß protein and the TupA Co-Regulator Bind to Protein Kinase A Tpk2 to Act as Antagonistic Molecular Switches of Fungal Morphological Changes The human pathogenic fungus Paracoccidioides brasiliensis (Pb) undergoes a morphological transition from a saprobic mycelium to pathogenic yeast that is controlled by the cAMP-signaling pathway. There is a change in the expression of the Gß-protein PbGpb1, which interacts with adenylate cyclase, during this morphological transition. We exploited the fact that the cAMP-signaling pathway of Saccharomyces cerevisiae does not include a Gß-protein to probe the functional role of PbGpb1. We present data that indicates that PbGpb1 and the transcriptional regulator PbTupA both bind to the PKA protein PbTpk2. PbTPK2 was able to complement a TPK2? strain of S. cerevisiae, XPY5a/a, which was defective in pseudohyphal growth. Whilst PbGPB1 had no effect on the parent S. cerevisiae strain, MLY61a/a, it repressed the filamentous growth of XPY5a/a transformed with PbTPK2, behaviour that correlated with a reduced expression of the floculin FLO11. In vitro, PbGpb1 reduced the kinase activity of PbTpk2, suggesting that inhibition of PbTpk2 by PbGpb1 reduces the level of expression of Flo11, antagonizing the filamentous growth of the cells. In contrast, expressing the co-regulator PbTUPA in XPY5a/a cells transformed with PbTPK2, but not untransformed cells, induced hyperfilamentous growth, which could be antagonized by co-transforming the cells with PbGPB1. PbTUPA was unable to induce the hyperfilamentous growth of a FLO8? strain, suggesting that PbTupA functions in conjunction with the transcription factor Flo8 to control Flo11 expression. Our data indicates that P. brasiliensis PbGpb1 and PbTupA, both of which have WD/ß-propeller structures, bind to PbTpk2 to act as antagonistic molecular switches of cell morphology, with PbTupA and PbGpb1 inducing and repressing filamentous growth, respectively. Our findings define a potential mechanism for controlling the morphological switch that underpins the virulence of dimorphic fungi. This work was supported by grants from the Wellcome Trust 069445, and GC and DC were the recipients of Wellcome Trust travelling fellowships. (Wellcome.ac.uk.) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Databáze: | OpenAIRE |
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