The Protein Phosphatase 2C Domain Contributes to The Pathobiological Function of Adenylyl Cyclase in Cryptococcus neoformans
Jae-Hyung Jin1, Myung Kyung Choi2, Kyung-Tae Lee3, Hyun-Soo Cho2 and Yong-Sun Bahn1*
1Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
2Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
3Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea
The cAMP signaling pathway governs growth, differentiation, stress response and adaptation, and the pathogenicity of plant and animal fungal pathogens. The central component of the cAMP pathway is adenylyl cyclase (AC), which produces cAMP in response to external signal and subsequently activates protein kinase A (PKA) to regulate its downstream effector proteins. The AC consists of multiple protein domains, including Ga-binding domain, Ras-associated domain, leucin-rich repeat, protein phosphatase 2C (PP2C), and AC-catalytic domain. Yet the function of the PP2C domain in AC remains unknown in most fungal pathogens. Here we functionally characterize the PP2C domain in the AC (Cac1) of Cryptococcus neoformans, which causes life-threatening human fungal meningoencephalitis in worldwide. To this end, we constructed C. neoformans strains containing CAC1PPD and CAC1ACD alleles, in which the PP2C and AC catalytic domains are deleted, respectively, and performed comparative phenotypic analysis in comparison with the wild-type and control strains. As expected, the AC catalytic domain is required for all the functions of Cac1 in C. neoformans: production of melanin and capsule, sexual differentiation, and stress response and adaptation. Surprisingly, however, we found that the PP2C domain plays a partial role in melanin and capsule production. In conclusion, here we demonstrate that the PP2C domain contributes to the function of Cac1 in virulence factor regulation of C. neoformans.