Endocytosis of EphA receptors is essential for the proper development of the retinocollicular topographic map

EMBO J. 2011 Apr 20;30(8):1593-607. doi: 10.1038/emboj.2011.44. Epub 2011 Feb 22.

Abstract

Endocytosis of Eph-ephrin complexes may be an important mechanism for converting cell-cell adhesion to a repulsive interaction. Here, we show that an endocytosis-defective EphA8 mutant forms a complex with EphAs and blocks their endocytosis in cultured cells. Further, we used bacterial artificial chromosome transgenic (Tg) mice to recapitulate the anterior>posterior gradient of EphA in the superior colliculus (SC). In mice expressing the endocytosis-defective EphA8 mutant, the nasal axons were aberrantly shifted to the anterior SC. In contrast, in Tg mice expressing wild-type EphA8, the nasal axons were shifted to the posterior SC, as predicted for the enhanced repellent effect of ephrinA reverse signalling. Importantly, Rac signalling was shown to be essential for EphA-ephrinA internalization and the subsequent nasal axonal repulsion in the SC. These results indicate that endocytosis of the Eph-ephrin complex is a key mechanism by which axonal repulsion is generated for proper guidance and topographic mapping.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Blotting, Western
  • Cells, Cultured
  • Endocytosis / physiology*
  • Fluorescent Antibody Technique
  • Humans
  • Immunoprecipitation
  • Mice
  • Mice, Transgenic
  • Neurons / cytology*
  • Neurons / metabolism
  • RNA, Messenger / genetics
  • Receptor, EphA8 / physiology*
  • Retinal Ganglion Cells / cytology*
  • Retinal Ganglion Cells / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Superior Colliculi / cytology*
  • Superior Colliculi / metabolism
  • Visual Pathways
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism

Substances

  • RNA, Messenger
  • Receptor, EphA8
  • rac GTP-Binding Proteins