Sho1 and msb2 play complementary but distinct roles in stress responses, sexual differentiation, and pathogenicity of cryptococcus neoformans

Yee Seul So, Juyeong Jang, Goun Park, Jintao Xu, Michal A. Olszewski, Yong Sun Bahn

Research output: Contribution to journalArticlepeer-review

Abstract

The high-osmolarity glycerol response (HOG) pathway is pivotal in environmental stress response, differentiation, and virulence of Cryptococcus neoformans, which causes fatal meningoencephalitis. A putative membrane sensor protein, Sho1, has been postulated to regulate HOG pathway, but its regulatory mechanism remains elusive. In this study, we characterized the function of Sho1 with relation to the HOG pathway in C. neoformans. Sho1 played minor roles in osmoresistance, thermotolerance, and maintenance of membrane integrity mainly in a HOG-independent manner. However, it was dispensable for cryostress resistance, primarily mediated through the HOG pathway. A mucin-like transmembrane (TM) protein, Msb2, which interacts with Sho1 in Saccharomyces cerevisiae, was identified in C. neoformans, but found not to interact with Sho1. MSB2 codeletion with SHO1 further decreased osmoresistance and membrane integrity, but not thermotolerance, of sho1 A mutant, indicating that both factors play to some level redundant but also discrete roles in C. neoformans. Sho1 and Msb2 played redundant roles in promoting the filamentous growth in sexual differentiation in a Cpk1-independent manner, in contrast to the inhibitory effect of the HOG pathway in the process. However, both factors contributed independently to Cpk1 phosphorylation during vegetative growth and endoplasmic reticulum (ER) stress response. Finally, Sho1 and Msb2 play distinct but complementary roles in the pulmonary virulence of C. neoformans. Overall, Sho1 and Msb2 play complementary but distinct roles in stress response, differentiation, and pathogenicity of C. neoformans.

Original languageEnglish
Article number2958
Pages (from-to)1-16
Number of pages16
JournalFrontiers in Endocrinology
Volume9
DOIs
Publication statusPublished - 2018

Bibliographical note

Funding Information:
This work was supported by National Research Foundation (NRF) grants funded by the Korea government (MSIT) (2016R1E1A1A01943365 and 2018R1A5A1025077) and in part by the Strategic Initiative for Microbiomes in Agriculture and Food funded by Ministry of Agriculture, Food and Rural Affairs (918012-4 to Y-SB). This study was also supported by US Department of Veteran’s Affairs Grants (I01BX000656 and IK6BX003615-01 to MO).

Funding Information:
This work was supported by National Research Foundation (NRF) grants funded by the Korea government (MSIT) (2016R1E1A1A01943365 and 2018R1A5A1025077) and in part by the Strategic Initiative for Microbiomes in Agriculture and Food funded by Ministry of Agriculture, Food and Rural Affairs (918012-4 to Y-SB). This study was also supported by US Department of Veteran?s Affairs Grants (I01BX000656 and IK6BX003615-01 to MO).

Publisher Copyright:
© 2018 So, Jang, Park, Xu, Olszewski and Bahn.

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism

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