title: Exosomes mediate cell contact-independent ephrin-Eph signaling during axon guidance.
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.
authors.affiliation: Max Planck Institute of Neurobiology, 82152 Martinsried, Germany Munich Cluster for Systems Neurology (SyNergy), 80336 Munich, Germany.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Gong
authors.affiliation: Max Planck Institute of Biochemistry, 82152 Martinsried, Germany Munich Cluster for Systems Neurology (SyNergy), 80336 Munich, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Körner
authors.affiliation: Max Planck Institute of Neurobiology, 82152 Martinsried, Germany.
authors.forename: Louise
authors.initials: L
authors.lastname: Gaitanos
authors.affiliation: Max Planck Institute of Neurobiology, 82152 Martinsried, Germany Munich Cluster for Systems Neurology (SyNergy), 80336 Munich, Germany rklein@neuro.mpg.de.
authors.forename: Rüdiger
authors.identifier: 0000-0002-3109-0163
authors.initials: R
authors.lastname: Klein
mesh_terms: D000818:Animals; D000071437:Axon Guidance; D002450:Cell Communication; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D036342:Ephrins / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008564:Membrane Potentials; D051379:Mice; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D040901:Proteomics; D036081:Receptors, Eph Family / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D036342:Ephrins; D019000:Phosphotyrosine; D036081:Receptors, Eph Family