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

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Gong,  Jingyi
Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society;

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Körner,  Roman
Hartl, Franz-Ulrich / Cellular Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society;

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Gaitanos,  Louise
Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society;

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Klein,  Rüdiger
Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society;

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Citation

Gong, J., Körner, R., Gaitanos, L., & Klein, R. (2016). Exosomes mediate cell contact-independent ephrin-Eph signaling during axon guidance. The Journal of Cell Biology, 214(1), 35-44. doi:10.1083/jcb.201601085.


Cite as: https://hdl.handle.net/11858/00-001M-0000-002D-41E8-6
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.