Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada
Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada.
J Cell Sci. 2021 Mar 29;134(6):jcs254359. doi: 10.1242/jcs.254359.
Vimentin is a structural protein that is required for mesenchymal cell migration and directly interacts with actin, β1 integrin and paxillin. We examined how these interactions enable vimentin to regulate cell migration on collagen. In fibroblasts, depletion of vimentin increased talin-dependent activation of β1 integrin by more than 2-fold. Loss of vimentin was associated with reduction of β1 integrin clustering by 50% and inhibition of paxillin recruitment to focal adhesions by more than 60%, which was restored by vimentin expression. This reduction of paxillin was associated with 65% lower Cdc42 activation, a 60% reduction of cell extension formation and a greater than 35% decrease in cell migration on collagen. The activation of PAK1, a downstream effector of Cdc42, was required for vimentin phosphorylation and filament maturation. We propose that vimentin tunes cell migration through collagen by acting as an adaptor protein for focal adhesion proteins, thereby regulating β1 integrin activation, resulting in well-organized, mature integrin clusters.This article has an associated First Person interview with the first author of the paper.
波形蛋白是一种结构蛋白，对于间充质细胞迁移是必需的，并且可以直接与肌动蛋白、β1 整合素和桩蛋白相互作用。我们研究了这些相互作用如何使波形蛋白能够调节细胞在胶原蛋白上的迁移。在成纤维细胞中，波形蛋白的耗竭使 β1 整合素依赖于 talin 的激活增加了两倍以上。波形蛋白的缺失与 β1 整合素簇减少 50%和桩蛋白向焦点黏附募集减少 60%有关，而波形蛋白的表达可以恢复这一作用。paxillin 的这种减少与 Cdc42 激活降低 65%、细胞延伸形成减少 60%和细胞在胶原蛋白上迁移增加 35%以上有关。Cdc42 的下游效应物 PAK1 的激活对于波形蛋白的磷酸化和丝束成熟是必需的。我们提出，波形蛋白通过充当焦点黏附蛋白的衔接蛋白来调节 β1 整合素的激活，从而调节细胞迁移，从而在胶原蛋白上形成组织良好的成熟整合素簇。本文附有对该论文第一作者的第一人称采访。
