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Endocytosis of EphA receptors is essential for the proper development of the retinocollicular topographic map
Author(s) -
Yoo Sooyeon,
Kim Yujin,
Noh Hyuna,
Lee Haeryung,
Park Eunjeong,
Park Soochul
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.44
Subject(s) - biology , endocytosis , receptor , neuroscience , anatomy , genetics
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.