EPH-ephrin mediated repulsion of cells

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R-HSA-3928665
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Homo sapiens
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Despite high-affinity multimeric interaction between EPHs and ephrins (EFNs), the cellular response to EPH-EFN engagement is usually repulsion between the two cells and signal termination. These repulsive responses induce an EPH receptor-expressing cell to retract from an ephrin-expressing cell after establishing initial contact. The repulsive responses mediated by EPH receptors in the growth cone at the leading edge of extending axons and in axonal collateral branches contribute to the formation of selective neuronal connections. It is unclear how high affinity trans-cellular interactions between EPHs and ephrins are broken to convert adhesion into repulsion. Two possible mechanisms have been proposed for the repulsion of EPH-EFN bearing cells: the first one involves regulated cleavage of ephrin ligands or EPH receptors by transmembrane proteases following cell-cell contact, while the second one is rapid endocytosis of whole EPH:EFN complexes during the retraction of the interacting cells or neuronal growth cones (Egea & Klein 2007, Janes et al. 2005). RAC also plays an essential role during growth cone collapse by promoting actin polymerization that drives membrane internalization by endocytosis (Marston et al. 2003).

Literature References
PubMed ID Title Journal Year
10958785 Regulated cleavage of a contact-mediated axon repellent

Hattori, M, Osterfield, M, Flanagan, JG

Science 2000
12973357 Rac-dependent trans-endocytosis of ephrinBs regulates Eph-ephrin contact repulsion

Marston, DJ, Dickinson, S, Nobes, CD

Nat. Cell Biol. 2003
17420126 Bidirectional Eph-ephrin signaling during axon guidance

Egea, J, Klein, R

Trends Cell Biol. 2007
18713744 Ephrin-B2-induced cleavage of EphB2 receptor is mediated by matrix metalloproteinases to trigger cell repulsion

Lin, KT, Sloniowski, S, Ethell, DW, Ethell, IM

J. Biol. Chem. 2008
16239146 Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans

Janes, PW, Saha, N, Barton, WA, Kolev, MV, Wimmer-Kleikamp, SH, Nievergall, E, Blobel, CP, Himanen, JP, Lackmann, M, Nikolov, DB

Cell 2005
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