Stx11, a member of the SNARE family, is generally expressed in immune cells. It mediates membrane fusion events, playing a role in processes like cytotoxic granule exocytosis at immunological synapses of CD8 T or NK cells, and is involved in pathways related to lipid metabolism, cell proliferation, and autophagy [3,4,5]. Genetic models, such as gene-knockout (KO) mouse models, are valuable for studying its functions.

In KO mouse models, restricting fatty acid supply, blocking fatty acid uptake, or inhibiting Stx11 palmitoylation attenuates muscle regeneration. This shows that dynamic palmitoylation of Stx11 controls injury-induced fatty acid uptake in muscle stem cells to promote muscle regeneration [1]. In the context of pulmonary fibrosis, overexpression of Stx11 in mice alleviates the condition by inhibiting fibroblast activation via the PI3K/AKT/mTOR pathway [2]. In Stx11-deficient mice, there is impaired CD4 T cell help for B cells, disrupted germinal center formation, reduced isotype class switching, and low antibody avidity, indicating its role in humoral immunity [5].

In conclusion, Stx11 is crucial for multiple biological processes. Its functions in muscle regeneration, pulmonary fibrosis, and humoral immunity have been revealed through model-based research, especially KO mouse models. These findings contribute to understanding the underlying mechanisms of related diseases and may provide potential therapeutic targets for conditions like muscle injury, pulmonary fibrosis, and immunodeficiency-related disorders.

References:

1. Wang, Juan, Li, Dong-Lin, Zheng, Lang-Fan, Li, Peng, Zhao, Tong-Jin. 2024. Dynamic palmitoylation of STX11 controls injury-induced fatty acid uptake to promote muscle regeneration. In Developmental cell, 59, 384-399.e5. doi:10.1016/j.devcel.2023.12.005. https://pubmed.ncbi.nlm.nih.gov/38198890/

2. Huang, Guichuan, Yang, Xiangsheng, Yu, Qingyang, Zhong, Nanshan, Tang, Xiao Xiao. 2024. Overexpression of STX11 alleviates pulmonary fibrosis by inhibiting fibroblast activation via the PI3K/AKT/mTOR pathway. In Signal transduction and targeted therapy, 9, 306. doi:10.1038/s41392-024-02011-y. https://pubmed.ncbi.nlm.nih.gov/39523374/

3. Canna, Scott W, Marsh, Rebecca A. . Pediatric hemophagocytic lymphohistiocytosis. In Blood, 135, 1332-1343. doi:10.1182/blood.2019000936. https://pubmed.ncbi.nlm.nih.gov/32107531/

4. Zhang, Gaojian, Han, Jianxiong, Wang, Lili, Ge, Honghua, Yang, Xingyuan. 2022. The vesicular transporter STX11 governs ATGL-mediated hepatic lipolysis and lipophagy. In iScience, 25, 104085. doi:10.1016/j.isci.2022.104085. https://pubmed.ncbi.nlm.nih.gov/35372814/

5. Kögl, Tamara, Chang, Hsin-Fang, Staniek, Julian, Aichele, Peter, Ammann, Sandra. 2024. Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect. In The Journal of experimental medicine, 221, . doi:10.1084/jem.20221122. https://pubmed.ncbi.nlm.nih.gov/38722309/