School of Chemistry, Raymond & Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel.
Center for Physics and Chemistry of Living Systems, Tel Aviv University, Tel Aviv, Israel.
Nat Commun. 2023 Feb 23;14(1):1037. doi: 10.1038/s41467-023-36596-9.
Migrasomes are newly discovered cell organelles forming by local swelling of retraction fibers. The migrasome formation critically depends on tetraspanin proteins present in the retraction fiber membranes and is modulated by the membrane tension and bending rigidity. It remained unknown how and in which time sequence these factors are involved in migrasome nucleation, growth, and stabilization, and what are the possible intermediate stages of migrasome biogenesis. Here using live cell imaging and a biomimetic system for migrasomes and retraction fibers, we reveal that migrasome formation is a two-stage process. At the first stage, which in biomimetic system is mediated by membrane tension, local swellings largely devoid of tetraspanin 4 form on the retraction fibers. At the second stage, tetraspanin 4 molecules migrate toward and onto these swellings, which grow up to several microns in size and transform into migrasomes. This tetraspanin 4 recruitment to the swellings is essential for migrasome growth and stabilization. Based on these findings we propose that the major role of tetraspanin proteins is in stabilizing the migrasome structure, while the migrasome nucleation and initial growth stages can be driven by membrane mechanical stresses.
迁移体是新发现的细胞细胞器，通过回缩纤维的局部肿胀形成。迁移体的形成严重依赖于存在于回缩纤维膜中的四跨膜蛋白，并受膜张力和弯曲刚度的调节。目前尚不清楚这些因素如何以及在哪个时间序列参与迁移体的成核、生长和稳定，以及迁移体生物发生的可能中间阶段是什么。在这里，我们使用活细胞成像和迁移体和回缩纤维的仿生系统，揭示了迁移体的形成是一个两阶段的过程。在第一阶段，在仿生系统中由膜张力介导，回缩纤维上形成了大量缺乏四跨膜蛋白 4 的局部肿胀。在第二阶段，四跨膜蛋白 4 分子向这些肿胀迁移，并生长到几微米大小，转化为迁移体。这种四跨膜蛋白 4 向肿胀的募集对于迁移体的生长和稳定是必不可少的。基于这些发现，我们提出四跨膜蛋白的主要作用是稳定迁移体的结构，而迁移体的成核和初始生长阶段可以由膜力学应力驱动。
