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

Journal of Cell Biology - Tập 214 Số 1 - Trang 35-44 - 2016
Jingyi Gong1,2, Roman Körner3,2, Louise Gaitanos1, Rüdiger Klein1,2
1Max Planck Institute of Neurobiology, 82152 Martinsried, Germany 1
2Munich Cluster for Systems Neurology (SyNergy), 80336 Munich, Germany 3
3Max Planck Institute of Biochemistry, 82152 Martinsried, Germany 2

Tóm tắt

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.

Từ khóa


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