Veltman Douwe M, Williams Thomas D, Bloomfield Gareth, Chen Bi-Chang, Betzig Eric, Insall Robert H, Kay Robert R
MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Beatson Institute for Cancer Research, Glasgow, United Kingdom.
Elife. 2016 Dec 13;5:e20085. doi: 10.7554/eLife.20085.
Macropinocytosis is a fundamental mechanism that allows cells to take up extracellular liquid into large vesicles. It critically depends on the formation of a ring of protrusive actin beneath the plasma membrane, which develops into the macropinocytic cup. We show that macropinocytic cups in are organised around coincident intense patches of PIP, active Ras and active Rac. These signalling patches are invariably associated with a ring of active SCAR/WAVE at their periphery, as are all examined structures based on PIP patches, including phagocytic cups and basal waves. Patch formation does not depend on the enclosing F-actin ring, and patches become enlarged when the RasGAP NF1 is mutated, showing that Ras plays an instructive role. New macropinocytic cups predominantly form by splitting from existing ones. We propose that cup-shaped plasma membrane structures form from self-organizing patches of active Ras/PIP, which recruit a ring of actin nucleators to their periphery.
巨胞饮作用是一种基本机制，它使细胞能够将细胞外液体摄入大囊泡中。它关键依赖于质膜下方形成的一圈突出的肌动蛋白，该肌动蛋白会发展成巨胞饮杯。我们发现，巨噬细胞的巨胞饮杯是围绕PIP、活性Ras和活性Rac的重合密集斑块组织起来的。这些信号斑块在其周边总是与一圈活性SCAR/WAVE相关联，所有基于PIP斑块检查的结构，包括吞噬杯和基底波，都是如此。斑块的形成不依赖于包围的F-肌动蛋白环，并且当RasGAP NF1发生突变时斑块会变大，这表明Ras起指导作用。新的巨胞饮杯主要通过从现有杯分裂形成。我们提出，杯状质膜结构由活性Ras/PIP的自组织斑块形成，这些斑块在其周边招募一圈肌动蛋白成核剂。
