Extension of O-Glycans, Mediated by Ktr3 and Cap6, respectively, is Critical for Cell Wall Integrity Signaling and Virulence in Cryptococcus neoformans
Eun Jung Thak, Dong-Jik Lee, Hyunah Kim, Ye Ji Son, Jung Ho Kim, Su-Bin Lee, Yong-Sun Bahn, Hyun Ah Kang
언어
영어(ENG)
URL
https://www.earticle.net/Article/A390460
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원문정보
초록
영어
The human fungal pathogen Cryptococcus neoformans assembles N-/O-linked glycans on its proteins in two types with and without xylose (1, 2). In this study, the CAP6 gene, encoding an α1,3-mannosyltransferase responsible for the second mannose addition to the minor O-glycans with xylose, was identified and functionally analyzed. The CAP6 deletion in the ktr3Δ strain, in which the α1,2-mannose addition to the major O-glycans is defected, resulted in almost complete blockage of O-glycan extension. Notably, the putative two cell surface sensor proteins, Wml (Wsc/Mid2-Like)1p and Wml2p, were shown to be subjected to minor and major O-mannosylation by Cap6 and Ktr3, respectively. The proteins levels of Wml1 and Wml2 were remarkably decreased in the ktr3Δ cap6Δ mutant, indicating that proper O-mannosylation is essential for their stability. The phosphorylation of Mpk1, induced by tunicamycin, was greatly decreased in the ktr3Δcap6Δ and the wml1Δwml2Δ, supporting an essential role of O-glycans on cell surface sensors in cell wall integrity signaling. As reflecting its defective growth under several stress conditions, the ktr3Δcap6Δ strain showed fully attenuated virulence in a mouse model of cryptococcosis. The delineation of the roles of protein glycosylation in fungal pathogenesis will not only provide a deep insight into the glycan-based fungal infection mechanism but also aid in the development of novel antifungal agents.
저자
Eun Jung Thak [ Department of Life Science, Chung-Ang University, Seoul, South Korea ]
Dong-Jik Lee [ Department of Life Science, Chung-Ang University, Seoul, South Korea ]
Hyunah Kim [ Department of Life Science, Chung-Ang University, Seoul, South Korea ]
Ye Ji Son [ Department of Life Science, Chung-Ang University, Seoul, South Korea ]
Jung Ho Kim [ Department of Life Science, Chung-Ang University, Seoul, South Korea ]
Su-Bin Lee [ Department of Life Science, Chung-Ang University, Seoul, South Korea ]
Yong-Sun Bahn [ Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South Korea ]
Hyun Ah Kang [ Department of Life Science, Chung-Ang University, Seoul, South Korea ]
본 학회는 화학, 생화학, 분자생물학, 미생물학, 식품공학, 의학, 약학, 유전공학 및 생물공학, 환경 및 기타 공업 등 전 분야의 탄수화물관련 이론과 기술을 연구 발전시키고 산학협동을 통해 이를 보급하여 국내 관련 산업의 발전 및 국민생활의 과학화에 기여하고자 하며, 이러한 목표와 비젼의 실현을 위해 회원들이 적극적인 참여와 활동을 전개하고자 한다.
간행물
간행물명
한국당과학회 학술대회
간기
연간
수록기간
2006~2022
십진분류
KDC 517DDC 614
이 권호 내 다른 논문 / 한국당과학회 학술대회 2020 한국당과학회 연례학술대회(온라인)