The palmitoylation of gasdermin D directs its membrane translocation and pore formation during pyroptosis

Balasubramanian, Arumugam; Hsu, Alan Y.; Ghimire, Laxman; Tahir, Muhammad; Devant, Pascal; Fontana, Pietro; Du, Gang; Liu, Xing; Dang, Fabin; Kambara, Hiroto; Xie, Xuemei; Liu, Fei; Hasegawa, Tomoya; Xu, Rong; Yu, Hongbo; Chen, Mei; Kolakowski, Steven; Trauger, Sunia A.; Larsen, Martin R.; Wei, Wenyi; Wu, Hao; Kagan, Jonathan C.; Lieberman, Judy; Luo, Hongbo R.

doi:10.1126/sciimmunol.adn1452

articleScience ImmunologyMar 26, 2024GREEN OA

The palmitoylation of gasdermin D directs its membrane translocation and pore formation during pyroptosis

ABArumugam Balasubramanian AYAlan Y. Hsu LGLaxman Ghimire MTMuhammad Tahir PDPascal Devant

Dana-Farber Cancer Institute · Dana-Farber/Harvard Cancer Center · +14 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Plasma membrane perforation elicited by caspase cleavage of the gasdermin D (GSDMD) N-terminal domain (GSDMD-NT) triggers pyroptosis. The mechanisms underlying GSDMD membrane translocation and pore formation are not fully understood. Here, using a proteomic approach, we identified fatty acid synthase (FASN) as a GSDMD-binding partner. S-palmitoylation of GSDMD at Cys 191 /Cys 192 (human/mouse), catalyzed by palmitoyl acyltransferases ZDHHC5 and ZDHHC9 and facilitated by reactive oxygen species (ROS), directly mediated membrane translocation of GSDMD-NT but not full-length GSDMD (GSDMD-FL). Palmitoylation of GSDMD-FL could be induced before inflammasome activation by stimuli such as lipopolysaccharide (LPS),…

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Topics & keywords

Topics

Keywords

Palmitoylation
Pyroptosis
Chromosomal translocation
Cell biology
Chemistry
Membrane
Endosome
Biology

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