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

Daliang Chen1, Thamarai K Janganan, Gongyou Chen

  • 1Centre for Infectious Diseases, Wolfson Research Institute, School of Biological and Biomedical Sciences, University of Durham - Queen's Campus, Stockton-on-Tees TS17 6BH, UK.

Molecular Microbiology
|July 20, 2007
PubMed

Insights

Paracoccidioides brasiliensis uses a cAMP-signalling pathway for its morphological switch. G protein interactions with adenylate cyclase (AC) regulate this crucial fungal transition.

Area of Science:

  • Medical Mycology
  • Cellular Signalling
  • Molecular Biology

Background:

  • Paracoccidioides brasiliensis undergoes a morphological transition from mycelium to yeast.
  • This dimorphic transition is regulated by the cyclic adenosine monophosphate (cAMP) signalling pathway.
  • Cellular cAMP levels increase during the transition to the yeast form.

Purpose of the Study:

  • To investigate the role of adenylate cyclase (AC) and G proteins in the morphological transition of P. brasiliensis.
  • To identify and characterize the genes encoding AC and G proteins involved in cAMP signalling.
  • To elucidate the novel signalling mechanism regulating the fungal morphological switch.

Main Methods:

  • Cloning of the cyr1 gene encoding adenylate cyclase (AC).
  • Cloning of genes encoding G alpha (Gpa1-3), G beta (Gpb1), and G gamma (Gpg1) proteins.
  • Analysis of gene transcript levels and protein interactions under different morphological conditions.

Main Results:

  • Transcript levels of cyr1 correlate with cellular cAMP levels.
  • Gpa1 and Gpb1 interact with each other and with AC, while Gpa2 and Gpa3 do not.
  • Differential expression of gpa1 and gpb1 during the morphological transition suggests a role in signal maintenance.

Conclusions:

  • A novel signalling mechanism involving differential modulation of AC activity by Gpa1 and Gpb1 regulates the P. brasiliensis morphological switch.
  • This mechanism is crucial for maintaining the signal over the extended period required for the transition.
  • Understanding this pathway offers insights into fungal pathogenesis and potential therapeutic targets.

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