한빛사 논문
Jae-Hyung Jin1,7, Kyung-Tae Lee1,7, Joohyeon Hong1, Dongpil Lee1, Eun-Ha Jang1, Jin-Young Kim1, Yeonseon Lee1, Seung-Heon Lee1, Yee-Seul So1, Kwang-Woo Jung1,6, Dong-Gi Lee1, Eunji Jeong1, Minjae Lee1, Yu-Byeong Jang1, Yeseul Choi1, Myung Ha Lee1, Ji-Seok Kim1, Seong-Ryong Yu1, Jin-Tae Choi1, Jae-Won La1, Haneul Choi1, Sun-Woo Kim1, Kyung Jin Seo1, Yelin Lee1, Eun Jung Thak2, Jaeyoung Choi3, Anna F. Averette4, Yong-Hwan Lee5, Joseph Heitman4, Hyun Ah Kang2, Eunji Cheong1 & Yong-Sun Bahn1,*
1Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
2Department of Life Science, College of Natural Science, Chung-Ang University, Seoul 06974, Korea.
3Smart Farm Research Center, Korea Institute of Science and Technology, Gangneung 25451, Korea.
4Departments of Molecular Genetics and Microbiology, Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
5Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea.
6Present address: Radiation Research Division, Korea Atomic Energy Research Institute, Jeongeup 56212, Korea.
7These authors contributed equally: Jae-Hyung Jin, Kyung-Tae Lee.
*Corresponding author
Abstract
Phosphatases, together with kinases and transcription factors, are key components in cellular signalling networks. Here, we present a systematic functional analysis of the phosphatases in Cryptococcus neoformans, a fungal pathogen that causes life-threatening fungal meningoencephalitis. We analyse 230 signature-tagged mutant strains for 114 putative phosphatases under 30 distinct in vitro growth conditions, revealing at least one function for 60 of these proteins. Large-scale virulence and infectivity assays using insect and mouse models indicate roles in pathogenicity for 31 phosphatases involved in various processes such as thermotolerance, melanin and capsule production, stress responses, O-mannosylation, or retromer function. Notably, phosphatases Xpp1, Ssu72, Siw14, and Sit4 promote blood-brain barrier adhesion and crossing by C. neoformans. Together with our previous systematic studies of transcription factors and kinases, our results provide comprehensive insight into the pathobiological signalling circuitry of C. neoformans.
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