V. cholerae MakA is a cholesterol-binding pore-forming toxin that induces non-canonical autophagy
| العنوان: | V. cholerae MakA is a cholesterol-binding pore-forming toxin that induces non-canonical autophagy |
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| المؤلفون: | Jia, Xiaotong, Knyazeva, Anastasia, Zhang, Yu, Castro-Gonzalez, Sergio, Nakamura, Shuhei, Carlson, Lars-Anders, Yoshimori, Tamotsu, Corkery, Dale, Wu, Yao-Wen, Professor |
| المصدر: | Journal of Cell Biology. 221(12) |
| مصطلحات موضوعية: | cholesterol-binding, MakA, non-canonical autophagy, pore-forming toxin, Vibrio Cholerae |
| الوصف: | Pore-forming toxins (PFTs) are important virulence factors produced by many pathogenic bacteria. Here, we show that the Vibrio cholerae toxin MakA is a novel cholesterol-binding PFT that induces non-canonical autophagy in a pH-dependent manner. MakA specifically binds to cholesterol on the membrane at pH < 7. Cholesterol-binding leads to oligomerization of MakA on the membrane and pore formation at pH 5.5. Unlike other cholesterol-dependent cytolysins (CDCs) which bind cholesterol through a conserved cholesterol-binding motif (Thr-Leu pair), MakA contains an Ile-Ile pair that is essential for MakA-cholesterol interaction. Following internalization, endosomal acidification triggers MakA pore-assembly followed by ESCRT-mediated membrane repair and V-ATPase-dependent unconventional LC3 lipidation on the damaged endolysosomal membranes. These findings characterize a new cholesterol-binding toxin that forms pores in a pH-dependent manner and reveals the molecular mechanism of host autophagy manipulation. |
| وصف الملف: | electronic |
| URL الوصول: | https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-200014 https://doi.org/10.1083/jcb.202206040 https://umu.diva-portal.org/smash/get/diva2:1701387/FULLTEXT01.pdf |
| قاعدة البيانات: | SwePub |
| تدمد: | 00219525 |
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| DOI: | 10.1083/jcb.202206040 |