Nature Neuroscience 9, 322 - 330 (2006)
Published online: 19 February 2006; | doi:10.1038/nn1655
Silencing of EphA3 through a cis interaction with ephrinA5Ricardo F Carvalho1, Martin Beutler2, Katharine J M Marler1, Bernd Knöll1, 3, Elena Becker-Barroso1, 3, R Heintzmann2, Tony Ng2
& Uwe Drescher11
Medical Research Council, Centre for Developmental Neurobiology, London SE1 1UL, UK. 2
Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Hospital Campus, London SE1 1UL, UK. 3
Present addresses: Institute for Cell Biology, Department of Molecular Biology, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany (B.K.) and The Lancet Neurology, 32 Jamestown Road, London NW1 7BY, UK (E.B.-B.).
Correspondence should be addressed to Uwe Drescher uwe.drescher@kcl.ac.uk EphAs and ephrinAs are expressed in multiple areas of the developing brain in overlapping countergradients, notably in the retina and tectum. Here they are involved in targeting retinal axons to their correct topographic position in the tectum. We have used truncated versions of EphA3, single–amino acid point mutants of ephrinA5 and fluorescence resonance energy transfer technology to uncover a cis interaction between EphA3 and ephrinA5 that is independent of the established ligand-binding domain of EphA3. This cis interaction abolishes the induction of tyrosine phosphorylation of EphA3 and results in a loss of sensitivity of retinal axons to ephrinAs in trans. Our data suggest that formation of this complex transforms the uniform expression of EphAs in the nasal part of the retina into a gradient of functional EphAs and has a key role in controlling retinotectal mapping.
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