Discovery of the migrasome, an organelle mediating release of cytoplasmic contents during cell migration

Abstract

Cells communicate with each other through secreting and releasing proteins and vesicles. Many cells can migrate. In this study, we report the discovery of migracytosis, a cell migration-dependent mechanism for releasing cellular contents, and migrasomes, the vesicular structures that mediate migracytosis. As migrating cells move, they leave long tubular strands, called retraction fibers, behind them. Large vesicles, which contain numerous smaller vesicles, grow on the tips and intersections of retraction fibers. These fibers, which connect the vesicles with the main cell body, eventually break, and the vesicles are released into the extracellular space or directly taken up by surrounding cells. Since the formation of these vesicles is migration-dependent, we named them “migrasomes”. We also found that cytosolic contents can be transported into migrasomes and released from the cell through migrasomes. We named this migration-dependent release mechanism “migracytosis”.

Migrasomes: a new organelle of migrating cells

“…At the tips of these thin extensions, membrane shedding can occur, leaving integrin-containing vesicles attached to the substrate along the migratory path [7,8]. Previously thought to be passively deposited cell remnants, Ma et al [9] provide evidence for the active transport of materials from the cell body to a specialized subcompartment within these fibers, called migrasomes. As the cell moves and the fibers retract, the migrasomes are released to function as a potentially new and structurally distinct category of exosome-like vesicles that transmit signals between migrating cells (Figure 1).…”

“…Interestingly, exosomes have been shown to induce cell migration and invasion in cancer models [11]. Proteomic analysis of purified migrasomes suggests that they are compositionally related to exosomes [9], and in particular are enriched in tetraspanins, membrane protein markers of MVBs. However, unlike exosomes, the released migrasomes are large in diameter (0.5-1.2 µm) and contain variable numbers of small internal vesicles.…”

“…Most important is to understand the function of migrasomes. One clue comes from striking time-lapse videos showing that other cells following in the path of their depositors can take up migrasomes [9]. Which signals are activated upon contact with and/or internalization of deposited migrasomes?…”

“…By time-lapse microscopy of migrating cells [9], migrasomes form as bulb-like structures at the tips of, or at the intersections between, retraction fibers. Importantly, these bulbs continue to grow in diameter, receiving cytosolic input continuously over an ~2 h period as the migrating cell advances.…”

Exosome secretion promotes chemotaxis of cancer cells

“…[12][13][14][15] A major function of exosomes appears to be promotion of cell motility. 6,10,[16][17][18] Thus, exosomes have been shown to promote cell protrusion formation, 16 adhesion, 6,19 and cell polarity. 20 In neutrophils, autocrine generation of bioactive lipids on exosomes enhances motility toward the chemoattractant N-formyL-MethionyL-LeucyL-Phenylalanine (fMLP).…”