image: Generative mechanism of migrasome. Migrasome biogenesis can be divided into two steps: (i) the initial sites formation includes the generation of SMS2 foci, the recruitment of PIP5K1A, the formation of PI(4,5)P2, the recruitment of RAB35 and the interaction between integrin and extracellular matrix (ECM). (ii) the stabilization and maturation step includes not only the formation of swelling induced by calcium, SYT1 and tension fluctuation, but also the accumulation of TEMA for stabilization and membrane expansion.
Credit: ©Science China Press
Migrasomes, newly discovered in 2015, are unique cellular structures formed along cell migration trails. These membrane vesicles (under 3 μm in diameter) act as a "miniature universe," carrying cargo such as nucleic acids, proteins, organelles and etc. They play dual roles as molecular messengers and functional hubs in processes such as organ development, immune regulation, and tumor metastasis, offering new insights into disease mechanisms and therapeutic strategies.
A review by Dr. Chen Yang’s group at Peking University, entitled "A Decade of Discovery: Tracing the Footmarks of Migrasomes, Unveiling the Footprints of Cells" (published in Science China Life Sciences), summarizes the formation mechanisms, cargos, functions, and advanced techniques of migrasomes characterization. The biogenesis of migrasomes could be divided into two stages. First, sphingomyelin synthase 2 (SMS2) clusters at pseudopodia to mark initial formation sites, followed by the assembly of the PI(4,5)P2-Rab35-integrin complex, which provides mechanical tension. Second, membrane tension and calcium-dependent SYT1 drive membrane swelling, while TSPAN4-enriched microdomains (TEMAs) enhance membrane stiffness to promote expansion and maturation.
Once released, migrasomes participate in diverse physiological processes, including organ development, tissue repair, blood vessel formation, blood clotting, and viral spread. The review highlights their dual roles in diseases: migrasomes can protect by removing damaged mitochondria or delivering beneficial signaling proteins, but they may also worsen disease conditions by transferring cytokines or other signaling molecules to recipient cells. Additionally, they show promise as non-invasive biomarkers for early disease diagnosis.
Advanced techniques have improved migrasome capture efficiency. Meanwhile, breakthroughs in live imaging enable real-time observation of migrasome dynamics in living organisms. As research progresses, migrasomes are expanding the boundaries of organelle studies and paving new paths for understanding diseases and precision medicine.
Despite the above progress, many questions remain. Future studies will focus on the role of retraction fibers in spatial release of cargoes, as well as their specific functions in physiological and pathological processes. Interdisciplinary collaboration and innovations in multi-omics, advanced microscopy, and bioengineering are key to unlocking migrasomes’ full potential in diagnostics and therapy.
Journal
Science China Life Sciences
Method of Research
Literature review