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.

Migrasomes 是新发现的细胞器，由回缩纤维的局部肿胀形成。migrasome 的形成主要取决于收缩纤维膜中存在的四跨膜蛋白，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以何种时间顺序参与迁移体的成核、生长和稳定，以及迁移体生物发生的可能中间阶段是什么。在这里使用活细胞成像和用于迁移体和收缩纤维的仿生系统，我们揭示了迁移体的形成是一个两阶段过程。在第一阶段，在仿生系统中由膜张力介导，局部肿胀在回缩纤维上主要缺乏四跨膜蛋白 4 形式。在第二阶段，四跨膜蛋白 4 分子向这些肿胀迁移并迁移到这些肿胀上，这些肿胀长到几微米大小并转化为迁移体。这种四跨膜蛋白 4 募集到肿胀处对于迁移体的生长和稳定至关重要。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结构，而迁移体成核和初始生长阶段可由膜机械应力驱动。