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The cAMP pathway is important for controlling the morphological switch to the pathogenic yeast form of Paracoccidioides brasiliensis.

  • Thamarai Janganan
    ,
  • Daliang Chen
    ,
  • Gongyou Chen
    ,
  • Everaldo R. Marques
    ,
  • Marcia R. Kress
    ,
  • Gustavo H. Goldman
  • Durham University
    ,
  • Nanjing Agricultural University
    ,
  • Universidade de São Paulo
Research Output:
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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.

Publication Information

Output type

Research Output:
Contribution to journal
Article
 Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 761-79

Journal (Volume, Issue Number)

Molecular Microbiology (Volume 65, Issue 3)

Publication milestones

  • Published - 30/08/2007

Publication status

Published - 30/08/2007

ISSN

0950-382X

Publication IDs

  • handle.net: 10547/622751
  • Scopus: 34447581093

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