Migrasomes, enriched with signaling molecules such as chemokines, cytokines and angiogenic factors, play a pivotal role in the spatially defined delivery of these molecules, influencing critical physiological processes including organ morphogenesis and angiogenesis. The mechanism governing the accumulation of signaling molecules in migrasomes has been elusive. In this study, we show that secretory proteins, including signaling proteins, are transported into migrasomes by secretory carriers via both the constitutive and regulated secretion pathways. During cell migration, a substantial portion of these carriers is redirected to the rear of the cell and actively transported into migrasomes, driven by the actin-dependent motor protein Myosin-5a. Once at the migrasomes, these carriers fuse with the migrasome membrane through SNARE-mediated mechanisms. Inhibiting migrasome formation significantly reduces secretion, suggesting migrasomes as a principal secretion route in migrating cells. Our findings reveal a specialized, highly localized secretion paradigm in migrating cells, conceptually paralleling the targeted neurotransmitter release observed in neuronal systems.

迁移体富含趋化因子、细胞因子和血管生成因子等信号分子，在这些分子的空间限定递送中发挥着关键作用，影响包括器官形态发生和血管生成在内的关键生理过程。控制迁移体中信号分子积累的机制一直难以捉摸。在这项研究中，我们发现分泌蛋白，包括信号蛋白，由分泌载体通过组成型和调节性分泌途径转运到迁移体中。在细胞迁移过程中，这些载体的很大一部分被重定向到细胞后部，并在肌动蛋白依赖性运动蛋白 Myosin-5a 的驱动下主动转运到迁移体中。一旦到达迁移体，这些载体就会通过 SNARE 介导的机制与迁移体膜融合。抑制迁移小体的形成显着减少分泌，表明迁移小体是迁移细胞的主要分泌途径。我们的研究结果揭示了迁移细胞中专门的、高度局部化的分泌模式，在概念上与神经元系统中观察到的靶向神经递质释放平行。