肌球蛋白 IIA 和形成蛋白依赖性丝状伪足黏附的机械敏感性。
Myosin IIA and formin dependent mechanosensitivity of filopodia adhesion.
机构信息
Mechanobiology Institute, National University of Singapore, T-lab, 5A Engineering Drive 1, Singapore, 117411, Singapore.
Center for BioImaging Sciences, National University of Singapore, 14 Science Drive 4, Singapore, 117557, Singapore.
出版信息
Nat Commun. 2019 Aug 9;10(1):3593. doi: 10.1038/s41467-019-10964-w.
Filopodia, dynamic membrane protrusions driven by polymerization of an actin filament core, can adhere to the extracellular matrix and experience both external and cell-generated pulling forces. The role of such forces in filopodia adhesion is however insufficiently understood. Here, we study filopodia induced by overexpression of myosin X, typical for cancer cells. The lifetime of such filopodia positively correlates with the presence of myosin IIA filaments at the filopodia bases. Application of pulling forces to the filopodia tips through attached fibronectin-coated laser-trapped beads results in sustained growth of the filopodia. Pharmacological inhibition or knockdown of myosin IIA abolishes the filopodia adhesion to the beads. Formin inhibitor SMIFH2, which causes detachment of actin filaments from formin molecules, produces similar effect. Thus, centripetal force generated by myosin IIA filaments at the base of filopodium and transmitted to the tip through actin core in a formin-dependent fashion is required for filopodia adhesion.
丝状伪足是由肌动蛋白丝聚合驱动的动态细胞膜突起，可以黏附在细胞外基质上，并同时承受外部和细胞产生的拉力。然而，这种力在丝状伪足黏附中的作用还不够清楚。在这里，我们研究了肌球蛋白 X 过表达诱导的丝状伪足，这是典型的癌细胞特征。这种丝状伪足的寿命与丝状伪足基部的肌球蛋白 IIA 纤维的存在呈正相关。通过附着的纤维连接蛋白包被的激光捕获珠向丝状伪足尖端施加拉力，导致丝状伪足持续生长。肌球蛋白 IIA 的药理学抑制或敲低会使丝状伪足与珠的黏附作用消失。formin 抑制剂 SMIFH2 会导致肌动蛋白丝从formin 分子上脱离，也会产生类似的效果。因此，丝状伪足基部的肌球蛋白 IIA 纤维产生的向心拉力通过formin 依赖性方式传递到丝状伪足的尖端，这对于丝状伪足的黏附是必需的。
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