Vimentin undergoes liquid-liquid phase separation to form droplets which wet and stabilize actin fibers

• 成果类型: Article
• 署名作者: Basu, Arkaprabha; Krug, Tommy; du Pont, Benjamin; Huang, Qiaoling; Sun, Sijie; Adam, Stephen A.; Goldman, Robert D.; Weitz, David A.
• 署名单位: Harvard University; Xiamen University; Northwestern University; Feinberg School of Medicine; Harvard University; Harvard University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11760
• DOI: 10.1073/pnas.2418624122
• 发表日期: 2025-03-11
• 关键词: microtubule-dependent transport; intermediate-filaments; persistence length; cell mechanics; ORGANIZATION; precursors; molecules; tetramers; protein

摘要

The cytoskeleton is composed of F- actin, microtubules, and intermediate filaments (IFs). Vimentin is one of the most ubiquitous and well- studied IFs. It is involved in many activities including wound healing, tissue fibrosis, and cancer metastasis, all of which require rapid vimentin IF assembly. In this paper, we report that vimentin forms liquid condensates which appear to enable rapid filament growth. Given the transient nature of these droplets, we focus on properties of vimentin- Y117L, which has a point mutation that leads to formation of condensates but not IFs, enabling us to study these droplets in detail. The droplets dissolve under 1,6- Hexanediol treatment and under decreasing concentration, confirming that they are liquid, and phase separated. These condensates extensively wet actin stress fibers, rendering them resistant to actin- binding drugs and protecting them from depolymerization. We show similar behavior occurs in wild- type vimentin during its assembly into filaments.