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TMED10-mediated unconventional secretion of IL-33 regulates intestinal epithelium differentiation and homeostasis

Cell Research volume 34, pages 258–261 (2024)Cite this article

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Dear Editor,

Unconventional protein secretion (UcPS) refers to the release of non-signal peptide-containing secretory proteins independent of the ER–Golgi trafficking.1 Although two major pathways including vesicle-dependent and -independent UcPS have been revealed,1 the physiological role of each pathway is largely unclear due to the lack of molecular details. Previously, we identified a translocation pathway termed transmembrane p24 trafficking protein 10 (TMED10)-channeled UcPS (THU), which regulates vesicle-dependent UcPS pathway.2,3 In THU, TMED10 is a protein translocator key for mediating secretory cargo translocation into the ER–Golgi intermediate compartment to initiate vesicle-dependent UcPS. The identification of TMED10 as a central player for UcPS allows us to employ genetic approaches to understand physiological function of UcPS.

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Fig. 1: TMED10 regulates the differentiation of secretory cell lineage and protects against colitis by regulating IL-33 protein secretion.

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Acknowledgements

We apologize that due to space limitation, some key references of unconventional secretion, TMEDs and intestinal epithelium differentiation were not included. The work is funded by Ministry of Science and Technology of the People’s Republic of China (2021YFA0804802), the National Natural Science Foundation of China (32225013; 31988101 (Y.-G.C.); 92254302; 32130023; 32061143009), Beijing Natural Science Foundation (JQ20028), Vanke Special Fund for Public Health and Health Discipline Development, Tsinghua University (2022Z82WKJ009) and Ministry of Science and Technology of the People’s Republic of China (2019YFA0508602), New Cornerstone Science Foundation (Xplorer Prize).

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Author notes

  1. These authors contributed equally: Yang Wang, Meimei Huang, Xiangyue Mu.

Authors and Affiliations

  1. State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Science, School of Life Sciences, Tsinghua University, Beijing, China

    Yang Wang, Meimei Huang, Xiangyue Mu, Wanlu Song, Qing Guo, Yuan Liu, Ye-Guang Chen & Liang Ge

  2. Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing, China

    Yang Wang, Xiangyue Mu, Qing Guo & Liang Ge

  3. State Key Laboratory of Membrane Biology, School of Pharmaceutical Sciences, Tsinghua University, Beijing, China

    Min Zhang

  4. School of Basic Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China

    Ye-Guang Chen

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  1. Yang Wang
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Contributions

Y.W., M.H., Y.L., M.Z., L.G. and Y.-G.C. conceived the experiments and wrote the manuscript. Y.W., M.H., X.M., W.S. and Q.G. performed experiments and collected and analyzed data.

Corresponding authors

Correspondence to Yuan Liu, Ye-Guang Chen or Liang Ge.

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The authors declare no competing interests.

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Wang, Y., Huang, M., Mu, X. et al. TMED10-mediated unconventional secretion of IL-33 regulates intestinal epithelium differentiation and homeostasis. Cell Res 34, 258–261 (2024). https://doi.org/10.1038/s41422-023-00891-3

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