Zdhhc7, encoding zinc finger DHHC-type palmitoyl transferase 7, is involved in protein S-palmitoylation, a post-translational modification. It plays a crucial role in multiple biological pathways such as autophagy, inflammasome activation, and cell signaling regulation, and is thus of great biological importance. Genetic models, like Zdhhc7 knockout (KO) mice, are valuable for studying its functions [1,2].

In various disease-related studies, Zdhhc7 KO mouse models have revealed its significance. In NLRP3-related disorders, Zdhhc7 knockout diminishes NLRP3-mediated inflammasome activation in macrophages as NLRP3 Cys126 palmitoylation by Zdhhc7 is critical for this activation [1]. In the context of autophagy, ATG16L1 S-palmitoylation by Zdhhc7 is essential for LC3 lipidation and autophagosome formation, and ATG16L1-KO HeLa cells show a defect in this process [2]. In a mouse model of inflammatory bowel disease, knockout of Zdhhc7 relieves the symptoms as it is involved in the palmitoylation-depalmitoylation cycle of STAT3 which promotes TH17 differentiation [3]. Also, in lipopolysaccharide-induced lethal septic shock, perturbation of GSDMD palmitoylation by Zdhhc7 suppresses pyroptosis, affecting mouse survival [4].

In conclusion, Zdhhc7 is essential for processes like inflammasome activation, autophagy, and cell signaling regulation through protein S-palmitoylation. Zdhhc7 KO mouse models have contributed to understanding its role in diseases such as NLRP3-related disorders, inflammatory bowel disease, and septic shock, providing potential therapeutic targets for these conditions.

References:

1. Yu, Tao, Hou, Dan, Zhao, Jiaqi, Linder, Maurine E, Lin, Hening. 2024. NLRP3 Cys126 palmitoylation by ZDHHC7 promotes inflammasome activation. In Cell reports, 43, 114070. doi:10.1016/j.celrep.2024.114070. https://pubmed.ncbi.nlm.nih.gov/38583156/

2. Wei, Fujing, Wang, Yu, Yao, Jia, Kong, Eryan, Yang, Aimin. 2024. ZDHHC7-mediated S-palmitoylation of ATG16L1 facilitates LC3 lipidation and autophagosome formation. In Autophagy, 20, 2719-2737. doi:10.1080/15548627.2024.2386915. https://pubmed.ncbi.nlm.nih.gov/39087410/

3. Zhang, Mingming, Zhou, Lixing, Xu, Yuejie, Linder, Maurine E, Lin, Hening. 2020. A STAT3 palmitoylation cycle promotes TH17 differentiation and colitis. In Nature, 586, 434-439. doi:10.1038/s41586-020-2799-2. https://pubmed.ncbi.nlm.nih.gov/33029007/

4. Zhang, Na, Zhang, Jian, Yang, Yuanxin, Tan, Li, Xu, Daichao. 2024. A palmitoylation-depalmitoylation relay spatiotemporally controls GSDMD activation in pyroptosis. In Nature cell biology, 26, 757-769. doi:10.1038/s41556-024-01397-9. https://pubmed.ncbi.nlm.nih.gov/38538834/