机械反馈通过 E-钙黏蛋白促进细胞集体迁移中的定向传感。
Mechanical feedback through E-cadherin promotes direction sensing during collective cell migration.
机构信息
Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA.
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037-1000, USA.
出版信息
Cell. 2014 May 22;157(5):1146-59. doi: 10.1016/j.cell.2014.03.045.
E-cadherin is a major homophilic cell-cell adhesion molecule that inhibits motility of individual cells on matrix. However, its contribution to migration of cells through cell-rich tissues is less clear. We developed an in vivo sensor of mechanical tension across E-cadherin molecules, which we combined with cell-type-specific RNAi, photoactivatable Rac, and morphodynamic profiling, to interrogate how E-cadherin contributes to collective migration of cells between other cells. Using the Drosophila ovary as a model, we found that adhesion between border cells and their substrate, the nurse cells, functions in a positive feedback loop with Rac and actin assembly to stabilize forward-directed protrusion and directionally persistent movement. Adhesion between individual border cells communicates direction from the lead cell to the followers. Adhesion between motile cells and polar cells holds the cluster together and polarizes each individual cell. Thus, E-cadherin is an integral component of the guidance mechanisms that orchestrate collective chemotaxis in vivo.
E-钙黏蛋白是一种主要的同型细胞间黏附分子，它抑制细胞在基质上的迁移运动。然而，它对细胞穿过富含细胞组织的迁移的贡献尚不清楚。我们开发了一种用于测量 E-钙黏蛋白分子间机械张力的体内传感器，我们将其与细胞类型特异性 RNAi、光活化 Rac 和形态动力学分析相结合，以研究 E-钙黏蛋白如何有助于细胞在其他细胞之间的集体迁移。我们使用果蝇卵巢作为模型，发现位于卵巢边缘的细胞与其基底细胞——滋养细胞之间的黏附作用与 Rac 和肌动蛋白组装一起，形成正反馈回路，从而稳定向前突起和定向持久运动。单个边缘细胞之间的黏附作用将方向从先导细胞传递给后续细胞。运动细胞和极性细胞之间的黏附作用将细胞簇固定在一起，并使每个细胞极化。因此，E-钙黏蛋白是协调体内集体趋化作用的指导机制的一个组成部分。
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