The RGS protein Crg2 regulates both pheromone and cAMP signalling in Cryptococcus neoformans.

Published

Journal Article

G proteins orchestrate critical cellular functions by transducing extracellular signals into internal signals and controlling cellular responses to environmental cues. G proteins typically function as switches that are activated by G protein-coupled receptors (GPCRs) and negatively controlled by regulator of G protein signalling (RGS) proteins. In the human fungal pathogen Cryptococcus neoformans, three G protein alpha subunits (Gpa1, Gpa2 and Gpa3) have been identified. In a previous study, we identified the RGS protein Crg2 involved in regulating the pheromone response pathway through Gpa2 and Gpa3. In this study, a role for Crg2 was established in the Gpa1-cAMP signalling pathway that governs mating and virulence. We show that Crg2 physically interacts with Gpa1 and crg2 mutations increase cAMP production. crg2 mutations also enhance mating filament hyphae production, but reduce cell-cell fusion and sporulation efficiency during mating. Although crg2 mutations and the Gpa1 dominant active allele GPA1(Q284L) enhanced melanin production under normally repressive conditions, virulence was attenuated in a murine model. We conclude that Crg2 participates in controlling both Gpa1-cAMP-virulence and pheromone-mating signalling cascades and hypothesize it may serve as a molecular interface between these two central signalling conduits.

Full Text

Duke Authors

Cited Authors

  • Xue, C; Hsueh, Y-P; Chen, L; Heitman, J

Published Date

  • October 2008

Published In

Volume / Issue

  • 70 / 2

Start / End Page

  • 379 - 395

PubMed ID

  • 18761692

Pubmed Central ID

  • 18761692

Electronic International Standard Serial Number (EISSN)

  • 1365-2958

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2958.2008.06417.x

Language

  • eng

Conference Location

  • England