A Gβ protein and the TupA co-regulator bind to protein kinase a Tpk2 to act as antagonistic molecular switches of fungal morphological changes

2.50
Hdl Handle:
http://hdl.handle.net/10547/622745
Title:
A Gβ protein and the TupA co-regulator bind to protein kinase a Tpk2 to act as antagonistic molecular switches of fungal morphological changes
Authors:
Janganan, Thamarai K.; Chen, Gongyou; Chen, Daliang; Menino, Joao F.; Rodrigues, Fernando; Borges-Walmsley, Maria Ines; Walmsley, Adrian R. ( 0000-0002-5136-0511 )
Abstract:
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 Gβ-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 Gβ-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 TPK2Δ strain of S. cerevisiae, XPY5a/α, which was defective in pseudohyphal growth. Whilst PbGPB1 had no effect on the parent S. cerevisiae strain, MLY61a/α, it repressed the filamentous growth of XPY5a/α 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/α 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 FLO8Δ 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/β-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.
Affiliation:
University of Durham; University of Minho
Citation:
Janganan TK, Chen G, Chen D, Menino JF, Rodrigues F, Borges-Walmsley MI, Walmsley, AR (2015) 'A Gβ protein and the TupA Co-Regulator Bind to Protein Kinase A Tpk2 to Act as Antagonistic Molecular Switches of Fungal Morphological Changes.', PLoS ONE, 10 (9), pp.-.
Publisher:
PLOS
Journal:
PLoS ONE
Issue Date:
3-Sep-2015
URI:
http://hdl.handle.net/10547/622745
DOI:
10.1371/journal.pone.0136866
PubMed ID:
26334875
Additional Links:
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136866
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
Biomedical and biological science

Full metadata record

DC FieldValue Language
dc.contributor.authorJanganan, Thamarai K.en
dc.contributor.authorChen, Gongyouen
dc.contributor.authorChen, Daliangen
dc.contributor.authorMenino, Joao F.en
dc.contributor.authorRodrigues, Fernandoen
dc.contributor.authorBorges-Walmsley, Maria Inesen
dc.contributor.authorWalmsley, Adrian R.en
dc.date.accessioned2018-06-20T10:59:34Z-
dc.date.available2018-06-20T10:59:34Z-
dc.date.issued2015-09-03-
dc.identifier.citationJanganan TK, Chen G, Chen D, Menino JF, Rodrigues F, Borges-Walmsley MI, Walmsley, AR (2015) 'A Gβ protein and the TupA Co-Regulator Bind to Protein Kinase A Tpk2 to Act as Antagonistic Molecular Switches of Fungal Morphological Changes.', PLoS ONE, 10 (9), pp.-.en
dc.identifier.issn1932-6203-
dc.identifier.pmid26334875-
dc.identifier.doi10.1371/journal.pone.0136866-
dc.identifier.urihttp://hdl.handle.net/10547/622745-
dc.description.abstractThe 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 Gβ-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 Gβ-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 TPK2Δ strain of S. cerevisiae, XPY5a/α, which was defective in pseudohyphal growth. Whilst PbGPB1 had no effect on the parent S. cerevisiae strain, MLY61a/α, it repressed the filamentous growth of XPY5a/α 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/α 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 FLO8Δ 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/β-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.en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urlhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136866en
dc.rightsGreen - can archive pre-print and post-print or publisher's version/PDF-
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectParacoccidioides brasiliensisen
dc.subjectPbGpb1en
dc.subjectcAMP-signaling pathwayen
dc.titleA Gβ protein and the TupA co-regulator bind to protein kinase a Tpk2 to act as antagonistic molecular switches of fungal morphological changesen
dc.typeArticleen
dc.contributor.departmentUniversity of Durhamen
dc.contributor.departmentUniversity of Minhoen
dc.identifier.journalPLoS ONEen
dc.date.updated2018-06-20T00:00:16Z-
This item is licensed under a Creative Commons License
Creative Commons
All Items in UOBREP are protected by copyright, with all rights reserved, unless otherwise indicated.