title: The cAMP pathway is important for controlling the morphological switch to the pathogenic yeast form of Paracoccidioides brasiliensis.
abstract: Paracoccidioides brasiliensis is a human pathogenic fungus that switches from a saprobic mycelium to a pathogenic yeast. Consistent with the morphological transition being regulated by the cAMP-signalling pathway, there is an increase in cellular cAMP levels both transiently at the onset (< 24 h) and progressively in the later stages (> 120 h) of the transition to the yeast form, and this transition can be modulated by exogenous cAMP. We have cloned the cyr1 gene encoding adenylate cyclase (AC) and established that its transcript levels correlate with cAMP levels. In addition, we have cloned the genes encoding three Galpha (Gpa1-3), Gbeta (Gpb1) and Ggamma (Gpg1) G proteins. Gpa1 and Gpb1 interact with one another and the N-terminus of AC, but neither Gpa2 nor Gpa3 interacted with Gpb1 or AC. The interaction of Gpa1 with Gpb1 was blocked by GTP, but its interaction with AC was independent of bound nucleotide. The transcript levels for gpa1, gpb1 and gpg1 were similar in mycelium, but there was a transient excess of gpb1 during the transition, and an excess of gpa1 in yeast. We have interpreted our findings in terms of a novel signalling mechanism in which the activity of AC is differentially modulated by Gpa1 and Gpb1 to maintain the signal over the 10 days needed for the morphological switch.
authors.affiliation: Centre for Infectious Diseases, Wolfson Research Institute, School of Biological and Biomedical Sciences, University of Durham - Queen's Campus, Stockton-on-Tees TS17 6BH, UK.
authors.forename: Daliang
authors.initials: D
authors.lastname: Chen
authors.forename: Thamarai K
authors.initials: TK
authors.lastname: Janganan
authors.forename: Gongyou
authors.initials: G
authors.lastname: Chen
authors.forename: Everaldo R
authors.initials: ER
authors.lastname: Marques
authors.forename: Marcia R
authors.initials: MR
authors.lastname: Kress
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Goldman
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Walmsley
authors.forename: M Inês
authors.initials: MI
authors.lastname: Borges-Walmsley
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D025282:Mycelium / Q000166:cytology / Q000187:drug effects; D010228:Paracoccidioides / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000472:pathogenicity*; D011485:Protein Binding / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020798:Two-Hybrid System Techniques
chemical_list: D005656:Fungal Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D003994:Bucladesine; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases