Mediator protein Ssn8 negatively regulates diverse physiological processes and is required for virulence in Cryptococcus neoformans
Date Issued
2010
Date
2010
Author(s)
Wang, Lin-Ing
Abstract
Cryptococcus neoformans is an important human pathogen and also a model for studying fungal physiology and differentiation. Our prior studies have showed that blue light negatively regulates filamentous growth during sexual differentiation via the Cwc1/Cwc2 complex. An Agrobacterium T-DNA insertional mutant AY18 identified in a suppressor screen restores mating filamentation and also dramatically derepress the production of monokaryotic filaments in the overexpressed CWC1 background. Further characterization determined that the disruption of a Saccharomyces cerevisiae SSN8 homologue is responsible for the phenotypes. Ssn8 is a member of the Mediator complex which connects RNA polymerase II and transcriptional regulators during the initiation process. S. cerevisiae SSN8, also named SRB11/UME3/RYE2/CYCC, is widely involved in diverse physiological processes, including sugar utilization, meiosis, and gene regulation in response to different stresses. To determine its roles in C. neoformans, ssn8 deletion mutants were generated in different strain backgrounds. In addition to mating and monokaryotic filamentation, Ssn8 also negatively regulates other processes including invasive growth, and in vitro production of capsule and melanin. Ssn8 is also required for the maintenance of cell wall structure and integrity and virulence. Based on the epistasis analysis, yeast two hybrid assay and gene expression study, we conclude that C. neoformans Ssn8 functions downstream the Cpk1-pheromone response pathway and also resides at one of major branch downstream the Cwc complex along the light-mediated filamentation pathway. Taken together, our studies demonstrate that the conserved Mediator protein Ssn8 functions as a global regulator which negatively regulates diverse physiological and developmental processes and is also required for the virulence in C. neoformans.
Subjects
Cryptococcus neoformans
SSN8
sexual development
light response
Type
thesis
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