20971202

not annotated - annotated - LINNAEUS only

Ste50 adaptor protein governs sexual differentiation of Cryptococcus neoformans via the pheromone-response MAPK signaling pathway.

The mitogen-activated protein kinase (MAPK) pathways control diverse cellular functions in pathogenic fungi, including sexual differentiation, stress response, and maintenance of cell wall integrity. Here we characterized a Cryptococcus neoformans gene, which is homologous to the yeast Ste50 that is known to play an important role in mating pheromone response and stress response as an adaptor protein to the Ste11 MAPK kinase kinase in Saccharomyces cerevisiae. The C. neoformans Ste50 was not involved in any of the stress responses or virulence factor production (capsule and melanin) that are controlled by the HOG and Ras/cAMP signaling pathways. However, Ste50 was required for mating in both serotype A and serotype D C. neoformans strains. The ste50Delta mutant was completely defective in cell-cell fusion and mating pheromone production. Double mutation of the STE50 gene blocked increased production of pheromone and the hyper-filamentation phenotype of cells deleted of the CRG1 gene, which encodes the RGS protein that negatively regulates pheromone responsive G-protein signaling via the MAPK pathway. Regardless of the presence of the basidiomycota-specific SH3 domains of Ste50 that are known to be required for full virulence of Ustilago maydis, Ste50 was dispensable for virulence of C. neoformans in a murine model of cryptococcosis. In conclusion, the Ste50 adaptor protein controls sexual differentiation of C. neoformans via the pheromone-responsive MAPK pathway but is not required for virulence.



Ann file

T1	Species 56 79	Cryptococcus neoformans

N1 Reference T1 Taxonomy:5207

T2 Species 357 380 Cryptococcus neoformans

N2 Reference T2 Taxonomy:5207

T3 Species 572 596 Saccharomyces cerevisiae

N3 Reference T3 Taxonomy:4932

T4 Species 602 615 C. neoformans

N4 Reference T4 Taxonomy:5207

T5 Species 834 844;860 873 serotype A C. neoformans

N5 Reference T5 Taxonomy:5207

T6 Species 849 873 serotype D C. neoformans

N6 Reference T6 Taxonomy:5207

T7 Species 1381 1396 Ustilago maydis

N7 Reference T7 Taxonomy:5270

T8 Species 1437 1450 C. neoformans

N8 Reference T8 Taxonomy:5207

T9 Species 1564 1577 C. neoformans

N9 Reference T9 Taxonomy:5207

T10 Out-of-scope 414 419 yeast

N10 Reference T10 Taxonomy:147537 Saccharomycotina