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Zinc-binding domain mediates pleiotropic functions of Yvh1 in Cryptococcus neoformans

  • Microbial Genetics, Genomics and Molecular Biology
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Abstract

Yvh1 is a dual-specificity phosphatase (DUSP) that is evolutionarily conserved in eukaryotes, including yeasts and humans. Yvh1 is involved in the vegetative growth, differentiation, and virulence of animal and plant fungal pathogens. All Yvh1 orthologs have a conserved DUSP catalytic domain at the N-terminus and a zinc-binding (ZB) domain with two zinc fingers (ZFs) at the C-terminus. Although the DUSP domain is implicated in the regulation of MAPK signaling in humans, only the ZB domain is essential for most cellular functions of Yvh1 in fungi. This study aimed to analyze the functions of the DUSP and ZB domains of Yvh1 in the human fungal pathogen Cryptococcus neoformans, whose Yvh1 (CnYvh1) contains a DUSP domain at the C-terminus and a ZB domain at the N-terminus. Notably, CnYvh1 has an extended internal domain between the two ZF motifs in the ZB domain. To elucidate the function of each domain, we constructed individual domain deletions and swapping strains by complementing the yvh1Δ mutant with wild-type (WT) or mutated YVH1 alleles and examined their Yvh1-dependent phenotypes, including growth under varying stress conditions, mating, and virulence factor production. Here, we found that the complementation of the yvh1Δ mutant with the mutated YVH1 alleles having two ZFs of the ZB domain, but not the DUSP and extended internal domains, restored the WT phenotypic traits in the yvh1Δ mutant. In conclusion, the ZB domain, but not the N-terminal DUSP domain, plays a pivotal role in the pathobiological functions of cryptococcal Yvh1.

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Acknowledgements

This work was supported by the Strategic Initiative for Microbiomes in Agriculture and Food funded by the Ministry of Agriculture, Food and Rural Affairs (918012-4) and, in part, by grants from the National Research Foundation of Korea (2016R1E1A1A01943365 and 2018R1A5A1025077) from the Ministry of Science and ICT. We would like to thank Editage (https://www.editage.co.kr) for English language editing.

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Authors and Affiliations

  1. Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea

    Jae-Hyung Jin & Yong-Sun Bahn

  2. Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea

    Myung Kyung Choi & Hyun-Soo Cho

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  1. Jae-Hyung Jin
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  2. Myung Kyung Choi
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Correspondence to Yong-Sun Bahn.

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Jin, JH., Choi, M.K., Cho, HS. et al. Zinc-binding domain mediates pleiotropic functions of Yvh1 in Cryptococcus neoformans. J Microbiol. 59, 658–665 (2021). https://doi.org/10.1007/s12275-021-1287-1

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