EphB-ephrinB Bi-Directional Endocytosis Terminates Adhesion Allowing Contact Mediated Repulsion

Nat Cell Biol. 2003 Oct;5(10):869-78. doi: 10.1038/ncb1045. Epub 2003 Sep 14.


Eph receptors and their membrane-associated ephrin ligands mediate cell-cell repulsion to guide migrating cells and axons. Repulsion requires that the ligand-receptor complex be removed from the cell surface, for example by proteolytic processing of the ephrin ectodomain. Here we show that cell contact-induced EphB-ephrinB complexes are rapidly endocytosed during the retraction of cells and neuronal growth cones. Endocytosis occurs in a bi-directional manner that comprises of full-length receptor and ligand complexes. Endocytosis is sufficient to promote cell detachment and seems necessary for axon withdrawal during growth cone collapse. Here, we show a mechanism for the termination of adhesion and the promotion of cell repulsion after intercellular (trans) interaction between two transmembrane proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / physiology*
  • Cell Communication / physiology*
  • Cells, Cultured
  • Coculture Techniques
  • Endocytosis / physiology*
  • Ephrin-B1 / genetics
  • Ephrin-B1 / metabolism*
  • Ephrin-B2 / genetics
  • Ephrin-B2 / metabolism*
  • Growth Cones / metabolism
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Neurons / cytology
  • Neurons / metabolism
  • Receptors, Eph Family / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism


  • Ephrin-B1
  • Ephrin-B2
  • Recombinant Fusion Proteins
  • Receptors, Eph Family