Liquid-like condensates mediate competition between actin branching and bundling

• 成果类型: Article
• 署名作者: Graham, Kristin; Chandrasekaran, Aravind; Wang, Liping; Yang, Noel; Lafer, Eileen M.; Rangamani, Padmini; Stachowiak, Jeanne C.
• 署名单位: University of Texas System; University of Texas Austin; University of California System; University of California San Diego; University of Texas System; University of Texas at San Antonio; University of Texas System; University of Texas Austin
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12152
• DOI: 10.1073/pnas.23091521.21
• 发表日期: 2024-01-16
• 关键词: aldrich-syndrome protein; vasodilator-stimulated phosphoprotein; arp2/3 complex; ena/vasp proteins; vasp; wasp; filopodia; networks; DYNAMICS; domain

摘要

Cellular remodeling of actin networks underlies cell motility during key morphological events, from embryogenesis to metastasis. In these transformations, there is an inherent competition between actin branching and bundling, because steric clashes among branches create a mechanical barrier to bundling. Recently, liquid-like condensates consisting purely of proteins involved in either branching or bundling of the cytoskeleton have been found to catalyze their respective functions. Yet in the cell, proteins that drive branching and bundling are present simultaneously. In this complex environment, which factors determine whether a condensate drives filaments to branch or become bundled? To answer this question, we added the branched actin nucleator, Arp2/3, to condensates composed of VASP, an actin bundling protein. At low actin to VASP ratios, branching activity, mediated by Arp2/3, robustly inhibited VASP-mediated bundling of filaments, in agreement with agent-based simulations. In contrast, as the actin to VASP ratio increased, addition of Arp2/3 led to formation of aster-shaped structures, in which bundled filaments emerged from a branched actin core, analogous to filopodia emerging from a branched lamellipodial network. These results demonstrate that multi-component, liquid-like condensates can modulate the inherent competition between bundled and branched actin morphologies, leading to organized, higher-order structures, similar to those found in motile cells