Lehrstuhl für Biophysik E27, Physik-Department, Technische Universität München, Garching, Germany and.
Laboratory of Molecular Physiology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20892.
Mol Biol Cell. 2022 Sep 1;33(10):ar91. doi: 10.1091/mbc.E21-11-0577. Epub 2022 Jul 13.
Actin bundles constitute important cytoskeleton structures and enable a scaffold for force transmission inside cells. Actin bundles are formed by proteins, with multiple F-actin binding domains cross-linking actin filaments to each other. Vasodilator-stimulated phosphoprotein (VASP) has mostly been reported as an actin elongator, but it has been shown to be a bundling protein as well and is found in bundled actin structures at filopodia and adhesion sites. Based on in vitro experiments, it remains unclear when and how VASP can act as an actin bundler or elongator. Here we demonstrate that VASP bound to membranes facilitates the formation of large actin bundles during polymerization. The alignment by polymerization requires the fluidity of the lipid bilayers. The mobility within the bilayer enables VASP to bind to filaments and capture and track growing barbed ends. VASP itself phase separates into a protein-enriched phase on the bilayer. This VASP-rich phase nucleates and accumulates at bundles during polymerization, which in turn leads to a reorganization of the underlying lipid bilayer. Our findings demonstrate that the nature of VASP localization is decisive for its function. The up-concentration based on VASP's affinity to actin during polymerization enables it to simultaneously fulfill the function of an elongator and a bundler.
肌动蛋白束构成了重要的细胞骨架结构，并为细胞内的力传递提供了支架。肌动蛋白束由蛋白质形成，多个 F-actin 结合域将肌动蛋白丝相互交联。血管扩张刺激磷蛋白 (VASP) 主要被报道为肌动蛋白延伸因子，但它也被证明是一种成束蛋白，并存在于丝状伪足和黏附部位的束状肌动蛋白结构中。基于体外实验，尚不清楚 VASP 何时以及如何作为肌动蛋白成束蛋白或延伸因子发挥作用。在这里，我们证明了与膜结合的 VASP 在聚合过程中促进了大的肌动蛋白束的形成。聚合的排列需要脂双层的流动性。双层内的流动性使 VASP 能够与纤维结合，并捕获和跟踪生长的尖端。VASP 本身在双层上相分离成富含蛋白质的相。在聚合过程中，这种富含 VASP 的相在束上成核和积累，这反过来又导致底层脂质双层的重组。我们的研究结果表明，VASP 定位的性质对其功能至关重要。基于 VASP 与肌动蛋白结合的亲和力，在聚合过程中进行的浓度增加使其能够同时发挥延伸因子和成束蛋白的功能。
