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J Cell Biol. 2016 Jul 4;214(1):35-44. doi: 10.1083/jcb.201601085. Epub 2016 Jun 27.

Exosomes mediate cell contact-independent ephrin-Eph signaling during axon guidance.

Author information

1
Max Planck Institute of Neurobiology, 82152 Martinsried, Germany Munich Cluster for Systems Neurology (SyNergy), 80336 Munich, Germany.
2
Max Planck Institute of Biochemistry, 82152 Martinsried, Germany Munich Cluster for Systems Neurology (SyNergy), 80336 Munich, Germany.
3
Max Planck Institute of Neurobiology, 82152 Martinsried, Germany.
4
Max Planck Institute of Neurobiology, 82152 Martinsried, Germany Munich Cluster for Systems Neurology (SyNergy), 80336 Munich, Germany rklein@neuro.mpg.de.

Abstract

The cellular release of membranous vesicles known as extracellular vesicles (EVs) or exosomes represents a novel mode of intercellular communication. Eph receptor tyrosine kinases and their membrane-tethered ephrin ligands have very important roles in such biologically diverse processes as neuronal development, plasticity, and pathological diseases. Until now, it was thought that ephrin-Eph signaling requires direct cell contact. Although the biological functions of ephrin-Eph signaling are well understood, our mechanistic understanding remains modest. Here we report the release of EVs containing Ephs and ephrins by different cell types, a process requiring endosomal sorting complex required for transport (ESCRT) activity and regulated by neuronal activity. Treatment of cells with purified EphB2(+) EVs induces ephrinB1 reverse signaling and causes neuronal axon repulsion. These results indicate a novel mechanism of ephrin-Eph signaling independent of direct cell contact and proteolytic cleavage and suggest the participation of EphB2(+) EVs in neural development and synapse physiology.

PMID:
27354374
PMCID:
PMC4932373
DOI:
10.1083/jcb.201601085
[Indexed for MEDLINE]
Free PMC Article

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