title: Endocytosis of EphA receptors is essential for the proper development of the retinocollicular topographic map.
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.
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Chungpa-Dong 2-Ka, Yongsan-Ku, Seoul, Korea.
authors.forename: Sooyeon
authors.initials: S
authors.lastname: Yoo
authors.forename: Yujin
authors.initials: Y
authors.lastname: Kim
authors.forename: Hyuna
authors.initials: H
authors.lastname: Noh
authors.forename: Haeryung
authors.initials: H
authors.lastname: Lee
authors.forename: Eunjeong
authors.initials: E
authors.lastname: Park
authors.forename: Soochul
authors.initials: S
authors.lastname: Park
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D036143:Receptor, EphA8 / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013477:Superior Colliculi / Q000166:cytology* / Q000378:metabolism; D014795:Visual Pathways; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D036143:Receptor, EphA8; D020744:rac GTP-Binding Proteins