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

Lipid-gated monovalent ion fluxes regulate endocytic traffic and support immune surveillance.
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DOI:
10.1126/science.aaw9544
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发表时间:
2020-01-17
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Grinstein S
Grinstein S
中科院分区:
其他
文献类型:
--
作者:
Freeman SA;Uderhardt S;Saric A;Collins RF;Buckley CM;Mylvaganam S;Boroumand P;Plumb J;Germain RN;Ren D;Grinstein S

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尽管细胞外液正在进行(大)胞饮作用,但内吞途径的体积保持不变。为了研究其潜在机制,我们使用高分辨率视频成像来分析巨噬细胞在体外和原位形成的巨脂质体的命运。 Na+ 是内化的主要阳离子渗透剂,通过两个孔道 (TPC) 离开内吞液泡,同时伴随着 Cl− 和渗透耦合水的平行流出。由此产生的收缩导致膜形成锯齿状,从而促进曲率感应蛋白的募集。这些蛋白质稳定肾小管并促进其伸长,驱动液泡重塑、受体回收和细胞器的分解。未能解决内化液体会损害常驻巨噬细胞的组织监视活动。因此,渗透压驱动的内膜表面积与体积比的增加促进了区室之间的交通,并有助于确保组织稳态。
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.
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