Tetraspanin 4 stabilizes membrane swellings and facilitates their maturation into migrasomes.
Tetraspanin 4 stabilizes membrane swellings and facilitates their maturation into migrasomes.
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DOI：
10.1038/s41467-023-36596-9
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发表时间：
2023-02-23
影响因子：
16.6
通讯作者：
Sorkin, Raya
中科院分区：
文献类型：
--
作者：
Dharan, Raviv;Huang, Yuwei;Cheppali, Sudheer Kumar;Goren, Shahar;Shendrik, Petr;Wang, Weisi;Qiao, Jiamei;Kozlov, Michael M.;Yu, Li;Sorkin, Raya
回缩体是由回缩纤维局部肿胀形成的新发现的细胞器。迁移体的形成严重依赖于存在于收缩纤维膜中的四联蛋白，并受膜张力和弯曲刚度的调节。目前尚不清楚这些因子如何以及在哪个时间序列中参与迁移小体的成核、生长和稳定，以及迁移小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偏头痛和收缩纤维的仿生系统，揭示偏头痛的形成是一个两个阶段的过程。在第一阶段，在仿生系统中是由膜张力介导的，在收缩纤维上形成局部肿胀，大部分缺乏四联蛋白4。在第二阶段，四联蛋白4分子向这些肿胀迁移，这些肿胀长到几微米大小，并转化为迁移体。这种四联蛋白4对肿胀的招募对于迁移体的生长和稳定是必不可少的。基于这些发现，我们提出四联蛋白的主要作用是稳定迁移小体的结构，而迁移小体的成核和初始生长阶段可以由膜机械应力驱动。迁移小体是在迁移细胞的收缩纤维中形成的信号细胞器。本文作者表明，偏头痛的形成有两个阶段：最初的局部膜肿胀成熟，并通过募集的四蛋白来稳定。
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 are signaling organelles that form in retraction fibers of migrating cells. Here authors show that migrasomes form by a two-stage process: an initial local membrane swelling matures and is stabilized by recruited tetraspanin proteins.
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