Blake Thomas C A, Gallop Jennifer L
Gurdon Institute and Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom; email:
Annu Rev Cell Dev Biol. 2023 Oct 16;39:307-329. doi: 10.1146/annurev-cellbio-020223-025210. Epub 2023 Jul 5.
Filopodia are dynamic cell surface protrusions used for cell motility, pathogen infection, and tissue development. The molecular mechanisms determining how and where filopodia grow and retract need to integrate mechanical forces and membrane curvature with extracellular signaling and the broader state of the cytoskeleton. The involved actin regulatory machinery nucleates, elongates, and bundles actin filaments separately from the underlying actin cortex. The refined membrane and actin geometry of filopodia, importance of tissue context, high spatiotemporal resolution required, and high degree of redundancy all limit current models. New technologies are improving opportunities for functional insight, with reconstitution of filopodia in vitro from purified components, endogenous genetic modification, inducible perturbation systems, and the study of filopodia in multicellular environments. In this review, we explore recent advances in conceptual models of how filopodia form, the molecules involved in this process, and our latest understanding of filopodia in vitro and in vivo.
丝状伪足是动态的细胞表面突起，用于细胞运动、病原体感染和组织发育。决定丝状伪足如何生长和回缩以及在何处生长和回缩的分子机制，需要将机械力和膜曲率与细胞外信号传导以及细胞骨架的整体状态整合起来。所涉及的肌动蛋白调节机制从下方的肌动蛋白皮质中分别使肌动蛋白丝成核、延长并捆绑在一起。丝状伪足精细的膜和肌动蛋白几何结构、组织环境的重要性、所需的高时空分辨率以及高度的冗余性都限制了当前的模型。新技术正在改善获得功能见解的机会，包括从纯化成分体外重建丝状伪足、内源性基因修饰、诱导性扰动系统以及在多细胞环境中对丝状伪足的研究。在这篇综述中，我们探讨了丝状伪足如何形成的概念模型的最新进展、参与这一过程的分子，以及我们对体外和体内丝状伪足的最新认识。
