Adenylyl cyclase-associated protein Aca1 regulates virulence and differentiation of Cryptococcus neoformans via the cyclic AMP-protein kinase A cascade.

Published

Journal Article

The evolutionarily conserved cyclic AMP (cAMP) signaling pathway controls cell functions in response to environmental cues in organisms as diverse as yeast and mammals. In the basidiomycetous human pathogenic fungus Cryptococcus neoformans, the cAMP pathway governs virulence and morphological differentiation. Here we identified and characterized adenylyl cyclase-associated protein, Aca1, which functions in parallel with the Galpha subunit Gpa1 to control the adenylyl cyclase (Cac1). Aca1 interacted with the C terminus of Cac1 in the yeast two-hybrid system. By molecular and genetic approaches, Aca1 was shown to play a critical role in mating by regulating cell fusion and filamentous growth in a cAMP-dependent manner. Aca1 also regulates melanin and capsule production via the Cac1-cAMP-protein kinase A pathway. Genetic epistasis studies support models in which Aca1 and Gpa1 are necessary and sufficient components that cooperate to activate adenylyl cyclase. Taken together, these studies further define the cAMP signaling cascade controlling virulence of this ubiquitous human fungal pathogen.

Full Text

Duke Authors

Cited Authors

  • Bahn, Y-S; Hicks, JK; Giles, SS; Cox, GM; Heitman, J

Published Date

  • December 2004

Published In

Volume / Issue

  • 3 / 6

Start / End Page

  • 1476 - 1491

PubMed ID

  • 15590822

Pubmed Central ID

  • 15590822

International Standard Serial Number (ISSN)

  • 1535-9778

Digital Object Identifier (DOI)

  • 10.1128/EC.3.6.1476-1491.2004

Language

  • eng

Conference Location

  • United States