Kudryashova Elena, Ulrichs Heidi, Shekhar Shashank, Kudryashov Dmitri S
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
Department of Physics, Emory University, Atlanta, GA 30322, USA.
Sci Adv. 2022 Nov 16;8(46):eadc9239. doi: 10.1126/sciadv.adc9239. Epub 2022 Nov 18.
According to the cellular actin dynamics paradigm, filaments grow at their barbed ends and depolymerize predominantly from their pointed ends to form polar structures and do productive work. We show that actin can elongate at the pointed end when assisted by VopF/L toxins, which act as processive polymerases. In cells, processively moving VopF/L speckles are inhibited by factors blocking the pointed but not barbed ends. Multispectral single-molecule imaging confirmed that VopF molecules associate with the pointed end, actively promoting its elongation even in the presence of profilin. Consequently, VopF/L can break the actin cytoskeleton's polarity by compromising actin-based cellular processes. Therefore, actin filament design allows processive growth at both ends, which suggests unforeseen possibilities for cellular actin organization, particularly in specialized cells and compartments.
根据细胞肌动蛋白动力学范式，肌动蛋白丝在其带刺末端生长，并主要从其尖端末端解聚以形成极性结构并执行有效功能。我们发现，在作为持续性聚合酶的VopF/L毒素的辅助下，肌动蛋白可以在尖端末端伸长。在细胞中，持续移动的VopF/L斑点受到阻断尖端末端而非带刺末端的因素的抑制。多光谱单分子成像证实，VopF分子与尖端末端结合，即使在有肌动蛋白单体结合蛋白的情况下也能积极促进其伸长。因此，VopF/L可以通过损害基于肌动蛋白的细胞过程来打破肌动蛋白细胞骨架的极性。因此，肌动蛋白丝的设计允许两端进行持续生长，这表明细胞肌动蛋白组织存在不可预见的可能性，特别是在特化细胞和区室中。
