加拿大病童医院Sergio Grinstein、Spencer A. Freeman等研究人员合作发现脂质门控单价离子流调控内吞运输并促进免疫监视。相关论文2019年12月5日在线发表于国际学术期刊《科学》。

尽管胞外液（巨）胞饮作用的发生，但内吞途径的体积保持不变。为了研究潜在的机制，研究人员使用高分辨率的视频成像技术来分析巨噬细胞在体外和原位形成的巨胞饮体的命运。

内化的主要阳离子渗透剂Na离子通过两个孔道（TPC）离开胞吞液泡，同时伴随Cl离子和渗透耦合水的平行流出。产生的收缩引起膜的起皱，促进了曲率敏感蛋白的募集。这些蛋白质稳定了管腔并促进了它们的伸长，促使液泡重塑、受体再循环和细胞器的分解。无法实现內吞的液体损害了驻留巨噬细胞的组织监测活性。因此，渗透驱动的内膜表面体积比增加促进了隔室之间的运输并有助于确保组织的动态平衡。

附：英文原文

Title: Lipid-gated monovalent ion fluxes regulate endocytic traffic and support immune surveillance

Author: Spencer A. Freeman, Stefan Uderhardt, Amra Saric, Richard F. Collins, Catherine M. Buckley, Sivakami Mylvaganam, Parastoo Boroumand, Jonathan Plumb, Ronald N. Germain, Dejian Ren, Sergio Grinstein

Issue&Volume: 2019/12/05

Abstract: Despite ongoing (macro)pinocytosis of extracellular fluid, the volume of the endocytic pathway remains unchanged. To investigate the underlying mechanism, we used high-resolution video imaging to analyze the fate of macropinosomes formed by macrophages in vitro and in situ. Na+, the primary cationic osmolyte internalized, exited endocytic vacuoles via two pore channels (TPC), accompanied by parallel efflux of Cl and osmotically-coupled water. The resulting shrinkage caused crenation of the membrane which fostered recruitment of curvature-sensing proteins. These proteins stabilized tubules and promoted their elongation, driving vacuolar remodeling, receptor recycling, and resolution of the organelles. Failure to resolve internalized fluid impairs the tissue surveillance activity of resident macrophages. Thus, osmotically-driven increases in the surface-to-volume ratio of endomembranes promote traffic between compartments and help to ensure tissue homeostasis.

DOI: 10.1126/science.aaw9544

Source: https://science.sciencemag.org/content/early/2019/12/04/science.aaw9544