Antenna Mechanism of Length Control of Actin Cables

Actin cables are linear cytoskeletal structures that serve as tracks for myosin-based intracellular transport of vesicles and organelles in both yeast and mammalian cells. In a yeast cell undergoing budding, cables are in constant dynamic turnover yet some cables grow from the bud neck toward the back of the mother cell until their length roughly equals the diameter of the mother cell. This raises the question: how is the length of these cables controlled? Here we describe a novel molecular mechanism for cable length control inspired by recent experimental observations in cells. This “antenna mechanism” involves three key proteins: formins, which polymerize actin, Smy1 proteins, which bind formins and inhibit actin polymerization, and myosin motors, which deliver Smy1 to formins, leading to a length-dependent actin polymerization rate. We compute the probability distribution of cable lengths as a function of several experimentally tuneable parameters such as the formin-binding affinity of Smy1 and the concentration of myosin motors delivering Smy1. These results provide testable predictions of the antenna mechanism of actin-cable length control.

肌动蛋白束（actin cables）是一类线性细胞骨架结构，在酵母与哺乳动物细胞中，它们可作为基于肌球蛋白（myosin）的囊泡与细胞器胞内运输的轨道。在处于出芽阶段的酵母细胞中，肌动蛋白束始终处于动态周转状态，但部分束会从芽颈向母细胞后部延伸，直至其长度大致等于母细胞的直径。这一现象引出了一个关键科学问题：此类肌动蛋白束的长度是如何被精准调控的？本研究报道了一种受近期细胞实验观察启发的全新肌动蛋白束长度调控分子机制。该“天线机制”涉及三类关键蛋白：负责肌动蛋白聚合的成蛋白（Formins）、结合成蛋白并抑制肌动蛋白聚合的Smy1蛋白（Smy1 proteins），以及将Smy1蛋白递送至成蛋白的肌球蛋白马达，由此使得肌动蛋白聚合速率呈现长度依赖性。我们通过计算得到了肌动蛋白束长度的概率分布，该分布随若干实验可调控参数变化，例如Smy1蛋白的成蛋白结合亲和力，以及递送Smy1蛋白的肌球蛋白马达的浓度。上述结果为肌动蛋白束长度调控的天线机制提供了可被实验验证的理论预测。