Shedding light on the cell biology and diverse physiological functions of the migrasome

Abstract

The migrasome, an organelle that forms behind migrating cells, is connected to the cell body by a retraction fiber. Once released from the retraction fiber, the migrasome transforms into an extracellular vesicle and plays important roles in cell communication, development, angiogenesis, and disease. To date, the biogenesis, regulation of formation, cargo transportation, and physiological functions of migrasomes remain largely unknown. In this review, we summarize the current understanding of the mechanisms underlying migrasome formation and regulation, describe the evidence suggesting that migrasomes serve various physiological functions, compare the differences between migrasomes and other extracellular vesicles, emphasize the limitations in studying migrasomes, and discuss the potential of migrasomes in disease diagnosis and treatment.

Fig. 1

Properties of migrasomes. The migrasome is more likely formed at the branch point of RFs. It is enriched with small vesicles whose membranes contain high levels of Rab8a, VAMP2, VAMP3, and Caveolin-1. Additionally, macrodomains such as TSPANs, cholesterol, glycoproteins, and sphingomyelin are present on the migrasome membrane. Nucleic acids, chemokines, and morphogens are also enriched in the migrasome

Fig. 2

Mechanism for migrasome formation. SMS2 assembles into immobile foci at the leading edge; with the cell migrating forward, SMS2 is localized in RFs. SMS2 converts ceramide to sphingomyelin, allowing the swelling of the membrane at the SMS2 site

Fig. 3

Mechanisms for migrasome regulation. Overexpression of TSPANs and activation of the PI(4,5)P2–Rab35 and Ca²⁺–Syt-1 signaling pathways increase persistent cell migration and speed, resulting in enhanced migrasome formation