2006
DOI: 10.1038/nn1655
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Silencing of EphA3 through a cis interaction with ephrinA5

Abstract: 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. Thi… Show more

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Cited by 172 publications
(172 citation statements)
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“…Although we found that this ephrin-A5 þ SGN subpopulation reaches a peak at P0, knowing exactly whether this is a consistent subpopulation or whether type I SGNs are all expressing ephrin-A5 but at different times remains to be determined. Depending on the local neural network to be formed, recent work has shown that coexpressed Eph and ephrins cis-interact and mutually inactivate each other in the same cell, thereby fine-tuning the sensitivity of navigating axons to ephrins from the target tissue presented in trans [39][40][41] . Furthermore, the relative contribution of trans signalling and cis attenuation is influenced by the subcellular distribution of both ephrins and Ephs 39,42 .…”
Section: Discussionmentioning
confidence: 99%
“…Although we found that this ephrin-A5 þ SGN subpopulation reaches a peak at P0, knowing exactly whether this is a consistent subpopulation or whether type I SGNs are all expressing ephrin-A5 but at different times remains to be determined. Depending on the local neural network to be formed, recent work has shown that coexpressed Eph and ephrins cis-interact and mutually inactivate each other in the same cell, thereby fine-tuning the sensitivity of navigating axons to ephrins from the target tissue presented in trans [39][40][41] . Furthermore, the relative contribution of trans signalling and cis attenuation is influenced by the subcellular distribution of both ephrins and Ephs 39,42 .…”
Section: Discussionmentioning
confidence: 99%
“…One possibility is that the uniform expression of ephrin-A3 is manipulated into a functional gradient. For example, cis-interactions with graded EphA receptors could inactivate ephrin-A3 via a masking mechanism (Carvalho et al, 2006). Alternatively, if ephrin-A3 is acting as a receptor in the retina, it could be accompanied by a coreceptor expressed in a gradient.…”
Section: Ephrin-a3 Contributes To Topographic Map Formationmentioning
confidence: 99%
“…Within the ephrinA group, ephrinA5 has been extensively studied and was shown to be a ligand for EphA3 [11,12], EphA4 [13,14], EphA5 [10], EphA7 [15] and EphB2 [6] receptors. The study of its expression, mainly explored at the mRNA level in the rodent developing brain, has shown that ephrinA5 is present from early organogenesis [16] to postnatal stages throughout the central nervous system.…”
Section: Introductionmentioning
confidence: 99%