Figure 8: Proposed model for exosome control of directionally persistent in vivo cell migration
From: Directional cell movement through tissues is controlled by exosome secretion
(a) In the absence of exosome secretion, cells have unstable protrusions (blue arrows) and are unable to migrate effectively. (b) Secretion of exosomes (yellow) allows cells to effectively respond to directional cues by reinforcing nascent adhesions (orange) and stabilizing protrusions. (c) Positive feedback from exosomes promotes effective and directionally persistent motility, through adhesion enhancement and potentially additional unknown mechanisms. (d) ECM cargoes, such as FN, are carried on exosomes through a process involving endocytosis of ECM-integrin complexes, such as FN-α5β1, and subsequent sorting into MVEs. (e,f) Autocrine secretion of FN-coated exosomes at the leading edge may allow decoration of collagen fibrils with FN-bound exosomes that can then interact with cellular integrin receptors. Locally elevated concentration of FN-bound exosomes via secretion could facilitate integrin clustering and strong adhesion formation leading to accelerated migration. ECM carried on autocrine-secreted exosomes may be particularly effective at promoting cellular adhesion by matching matrix ligands to the adhesion receptor repertoire of the cell.
