Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
Center for Advanced Methods in Biological Image Analysis, Beckman Institute, California Institute of Technology, Pasadena, CA 91125.
Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27400-27411. doi: 10.1073/pnas.2007229117. Epub 2020 Oct 21.
Individual cell migration requires front-to-back polarity manifested by lamellipodial extension. At present, it remains debated whether and how membrane motility mediates this cell morphological change. To gain insights into these processes, we perform live imaging and molecular perturbation of migrating chick neural crest cells in vivo. Our results reveal an endocytic loop formed by circular membrane flow and anterograde movement of lipid vesicles, resulting in cell polarization and locomotion. Rather than clathrin-mediated endocytosis, macropinosomes encapsulate F-actin in the cell body, forming vesicles that translocate via microtubules to deliver actin to the anterior. In addition to previously proposed local conversion of actin monomers to polymers, we demonstrate a surprising role for shuttling of F-actin across cells for lamellipodial expansion. Thus, the membrane and cytoskeleton act in concert in distinct subcellular compartments to drive forward cell migration.
单个细胞的迁移需要通过片状伪足的延伸来表现前后极性。目前，关于膜流动性是否以及如何介导这种细胞形态变化仍存在争议。为了深入了解这些过程，我们在体内对迁移的鸡神经嵴细胞进行了实时成像和分子扰动。我们的结果揭示了一个由环形膜流和脂质小泡的正向运动形成的内吞循环，导致细胞极化和运动。这种内吞循环不是网格蛋白介导的内吞作用，而是大胞饮作用将 F-actin 包裹在细胞体中，形成通过微管转运到细胞前端的囊泡。除了先前提出的肌动蛋白单体在局部转化为聚合物之外，我们还证明了 F-actin 通过细胞穿梭在片状伪足扩展中的惊人作用。因此，膜和细胞骨架在不同的细胞区室中协同作用，推动细胞向前迁移。
