Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100084, China.
Center for Precision Medicine Multi-Omics Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Institute of Advanced Clinical Medicine, Peking University, Beijing 100191, China.
Proc Natl Acad Sci U S A. 2024 Jul 23;121(30):e2319267121. doi: 10.1073/pnas.2319267121. Epub 2024 Jul 15.
Migrasomes, vesicular organelles generated on the retraction fibers of migrating cells, play a crucial role in migracytosis, mediating intercellular communication. The cargoes determine the functional specificity of migrasomes. Migrasomes harbor numerous intraluminal vesicles, a pivotal component of their cargoes. The mechanism underlying the transportation of these intraluminal vesicles to the migrasomes remains enigmatic. In this study, we identified that Rab10 and Caveolin-1 (CAV1) mark the intraluminal vesicles in migrasomes. Transport of Rab10-CAV1 vesicles to migrasomes required the motor protein Myosin Va and adaptor proteins RILPL2. Notably, the phosphorylation of Rab10 by the kinase LRRK2 regulated this process. Moreover, CSF-1 can be transported to migrasomes through this mechanism, subsequently fostering monocyte-macrophage differentiation in skin wound healing, which served as a proof of the physiological importance of this transporting mechanism.
迁移小体是迁移细胞回缩纤维上产生的囊泡状细胞器,在细胞迁移中发挥关键作用,介导细胞间通讯。其内容物决定了迁移小体的功能特异性。迁移小体包含大量的腔囊泡,这是其内容物的关键组成部分。这些腔囊泡向迁移小体运输的机制仍不清楚。在这项研究中,我们发现 Rab10 和 Caveolin-1 (CAV1) 标记了迁移小体中的腔囊泡。Rab10-CAV1 囊泡向迁移小体的运输需要肌球蛋白 Va 和衔接蛋白 RILPL2。值得注意的是,激酶 LRRK2 对 Rab10 的磷酸化调节了这个过程。此外,CSF-1 可以通过这种机制被运输到迁移小体,随后促进皮肤伤口愈合中的单核细胞-巨噬细胞分化,这证明了这种运输机制的生理重要性。