引言
蛋白分泌作为细胞间信息传递的核心机制,在生物体的生命活动中扮演着不可或缺的角色。近年来,研究揭示越来越多的分泌蛋白缺乏信号肽,因此无法遵循传统的内质网-高尔基体分泌途径,这类分泌方式被称为非经典蛋白分泌(Unconventional protein secretion, UcPS)【1】。这些非经典分泌蛋白深度参与人体的发育、代谢以及炎症反应等生物学过程,且与神经退行性疾病、癌症等重大疾病紧密相关。因此,深入探究非经典分泌的分子机制对于理解这些疾病的病理机制至关重要。
非经典分泌途径主要涵盖膜泡运输和非膜泡运输两大类。其中,非经典分泌蛋白如何进入膜泡,特别是膜泡运输途径中的这一科学问题,仍是当前研究的热点和难点。基于前期研究,科学家们发现定位于内质网-高尔基体中间体(ER-Golgi intermediate compartment, ERGIC)的蛋白TMED10,能够形成同源寡聚体并调控一系列非经典分泌蛋白进入ERGIC【2】。这条由TMED10介导的非经典分泌途径被命名为TMED10通道化的非经典分泌(TMED10-Channeled UcPS, THU)。随后,THU的生理功能逐渐得到揭示,包括其在调控IL-33分泌、维护肠稳态和神经稳态中的作用【3,4】。
然而,THU在ERGIC上如何受到细胞内分子机器的调控,以及ERGIC如何区分其经典与非经典分泌功能,仍是亟待解决的问题。2024年6月26日,清华大学药学院张敏课题组和生命科学学院葛亮课题组在Nature Cell Biology期刊上发表了题为 A dual role of ERGIC-localized Rabs in TMED10-mediated unconventional protein secretion 的研究论文。该研究发现定位于ERGIC的Rab蛋白—Rab1和Rab2显著调控THU通路,并揭示了其具体作用机制。
![](http://image.uc.cn/s/wemedia/s/upload/2024/3077c3e3dba1a972660d8600e066dcd4.png)
参考文献
1. Malhotra, V., Unconventional protein secretion: an evolving mechanism. Embo Journal, 2013. 32(12): p. 1660-1664.2. Zhang, M., et al., A Translocation Pathway for Vesicle-Mediated Unconventional Protein Secretion. Cell, 2020. 181(3): p. 637-+.3. Wang, Y., et al., TMED10-mediated unconventional secretion of IL-33 regulates intestinal epithelium differentiation and homeostasis. Cell Research, 2024. 34(3): p. 258-261.4. Jiao, M.Y., et al., Active secretion of IL-33 from astrocytes is dependent on TMED10 and promotes central nervous system homeostasis. Brain Behavior and Immunity, 2024. 119: p. 539-553.5. Stenmark, H., Rab GTPases as coordinators of vesicle traffic. Nature Reviews Molecular Cell Biology, 2009. 10(8): p. 513-525.6. Saraste, J. and M. Marie, Intermediate compartment (IC): from pre-Golgi vacuoles to a semi-autonomous membrane system. Histochemistry and Cell Biology, 2018. 150(5): p. 407-430.7. Ge, L., et al., The ER-Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis. eLife, 2013. 2.8. Li, S.L., et al., A new type of ERGIC-ERES membrane contact mediated by TMED9 and SEC12 is required for autophagosome biogenesis. Cell Research, 2022. 32(2): p. 119-138.9. Sicari, D., et al., Role of the early secretory pathway in SARS-CoV-2 infection. Journal of Cell Biology, 2020. 219(9).https://www.nature.com/articles/s41556-024-01445-4责编|探索君
排版|探索君
文章来源|“BioArt”
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