A TrkB/EphrinA Interaction Controls Retinal Axon Branching and Synaptogenesis

Toward understanding topographically specific branching of retinal axons in their target area, we have studied the interaction between neurotrophin receptors and members of the Eph family. TrkB and its ligand BDNF are uniformly expressed in the retina and tectum, respectively, and exert a branch-pro...

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Autores: Marler, Katharine J. M., Becker-Barroso, Elena, Martínez, Albert, Llovera i Tomàs, Marta, Wentzel, Corinna, Poopalasundaram, Subathra, Hindges, Robert, Soriano, Eduardo, Comella i Carnicé, Joan Xavier, Drescher, Uwe
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2008
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/56688
Acesso em linha:https://doi.org/10.1523/JNEUROSCI.1915-08.2008
http://hdl.handle.net/10459.1/56688
Access Level:Acceso aberto
Palavra-chave:Axon guidance
BDNF
Neurotrophin
Topography
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spelling A TrkB/EphrinA Interaction Controls Retinal Axon Branching and SynaptogenesisMarler, Katharine J. M.Becker-Barroso, ElenaMartínez, AlbertLlovera i Tomàs, MartaWentzel, CorinnaPoopalasundaram, SubathraHindges, RobertSoriano, EduardoComella i Carnicé, Joan XavierDrescher, UweAxon guidanceBDNFNeurotrophinTopographyToward understanding topographically specific branching of retinal axons in their target area, we have studied the interaction between neurotrophin receptors and members of the Eph family. TrkB and its ligand BDNF are uniformly expressed in the retina and tectum, respectively, and exert a branch-promoting activity, whereas EphAs and ephrinAs are expressed in gradients in retina andtectum and can mediate a suppression of axonal branching.We have identified a novelcisinteraction between ephrinA5 and TrkB on retinal ganglion cell axons. TrkB interacts with ephrinA5 via its second cysteine-rich domain (CC2), which is necessary and sufficientfor bindingto ephrinA5. Their functional interaction is twofold: ephrinA5 augments BDNF-promoted retinal axon branching in the absence of its activator EphA7–Fc, whereas EphA7–Fc application abolishes branching in a local and concentration-dependent manner. The importance of TrkB in this process is shown by the fact that overexpression of an isolated TrkB–CC2 domain interfering with the ephrinA/TrkB interaction abolishes this regulatory interplay, whereas knockdown of TrkB via RNA interference diminishes the ephrinA5-evoked increase in branching. The ephrinA/Trk interaction is neurotrophin induced and specifically augments the PI-3 kinase/Akt pathway generally known to be involved in the promotion of branching. In addition, ephrinAs/TrkB modulate axon branching and also synapse formation of hippocampal neurons. Our findings uncover molecular mechanisms of how spatially restricted axon branching can be achieved by linking globally expressed branch-promoting with differentially expressed branch-suppressing activities. In addition, our data suggest that growth factors and the EphA– ephrinA system interact in a way that affects axon branching and synapse development.This work was supported by the Wellcome Trust, Biotechnology and Biological Sciences Research Council, and the Medical Research Council, as well as Ministerio de Educación y Ciencia (MEC) Grant SAF 2007-60287 and Generalitat de Catalunya to (J.C.), MEC Grant SAF2005-0171 (E.S.), Instituto de Salud Carlos III Grants PI04/2433 (A.M.) and P04/2537 (M.L.). M.L. holds a Ramon y Cajal research contract from the Spanish Ministry of Education and Science.Society for Neuroscience2008info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1523/JNEUROSCI.1915-08.2008http://hdl.handle.net/10459.1/56688reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésMIECI/PN2004-2007/SAF2007-60287MIECI/PN2004-2007/SAF2005-0171Reproducció del document publicat a https://doi.org/10.1523/JNEUROSCI.1915-08.2008The Journal of Neuroscience, 2008, vol. 28, núm. 48, p. 12700-12712(c) Society for Neuroscience, 2008info:eu-repo/semantics/openAccessoai:recercat.cat:10459.1/566882026-05-29T05:05:01Z
dc.title.none.fl_str_mv A TrkB/EphrinA Interaction Controls Retinal Axon Branching and Synaptogenesis
title A TrkB/EphrinA Interaction Controls Retinal Axon Branching and Synaptogenesis
spellingShingle A TrkB/EphrinA Interaction Controls Retinal Axon Branching and Synaptogenesis
Marler, Katharine J. M.
Axon guidance
BDNF
Neurotrophin
Topography
title_short A TrkB/EphrinA Interaction Controls Retinal Axon Branching and Synaptogenesis
title_full A TrkB/EphrinA Interaction Controls Retinal Axon Branching and Synaptogenesis
title_fullStr A TrkB/EphrinA Interaction Controls Retinal Axon Branching and Synaptogenesis
title_full_unstemmed A TrkB/EphrinA Interaction Controls Retinal Axon Branching and Synaptogenesis
title_sort A TrkB/EphrinA Interaction Controls Retinal Axon Branching and Synaptogenesis
dc.creator.none.fl_str_mv Marler, Katharine J. M.
Becker-Barroso, Elena
Martínez, Albert
Llovera i Tomàs, Marta
Wentzel, Corinna
Poopalasundaram, Subathra
Hindges, Robert
Soriano, Eduardo
Comella i Carnicé, Joan Xavier
Drescher, Uwe
author Marler, Katharine J. M.
author_facet Marler, Katharine J. M.
Becker-Barroso, Elena
Martínez, Albert
Llovera i Tomàs, Marta
Wentzel, Corinna
Poopalasundaram, Subathra
Hindges, Robert
Soriano, Eduardo
Comella i Carnicé, Joan Xavier
Drescher, Uwe
author_role author
author2 Becker-Barroso, Elena
Martínez, Albert
Llovera i Tomàs, Marta
Wentzel, Corinna
Poopalasundaram, Subathra
Hindges, Robert
Soriano, Eduardo
Comella i Carnicé, Joan Xavier
Drescher, Uwe
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Axon guidance
BDNF
Neurotrophin
Topography
topic Axon guidance
BDNF
Neurotrophin
Topography
description Toward understanding topographically specific branching of retinal axons in their target area, we have studied the interaction between neurotrophin receptors and members of the Eph family. TrkB and its ligand BDNF are uniformly expressed in the retina and tectum, respectively, and exert a branch-promoting activity, whereas EphAs and ephrinAs are expressed in gradients in retina andtectum and can mediate a suppression of axonal branching.We have identified a novelcisinteraction between ephrinA5 and TrkB on retinal ganglion cell axons. TrkB interacts with ephrinA5 via its second cysteine-rich domain (CC2), which is necessary and sufficientfor bindingto ephrinA5. Their functional interaction is twofold: ephrinA5 augments BDNF-promoted retinal axon branching in the absence of its activator EphA7–Fc, whereas EphA7–Fc application abolishes branching in a local and concentration-dependent manner. The importance of TrkB in this process is shown by the fact that overexpression of an isolated TrkB–CC2 domain interfering with the ephrinA/TrkB interaction abolishes this regulatory interplay, whereas knockdown of TrkB via RNA interference diminishes the ephrinA5-evoked increase in branching. The ephrinA/Trk interaction is neurotrophin induced and specifically augments the PI-3 kinase/Akt pathway generally known to be involved in the promotion of branching. In addition, ephrinAs/TrkB modulate axon branching and also synapse formation of hippocampal neurons. Our findings uncover molecular mechanisms of how spatially restricted axon branching can be achieved by linking globally expressed branch-promoting with differentially expressed branch-suppressing activities. In addition, our data suggest that growth factors and the EphA– ephrinA system interact in a way that affects axon branching and synapse development.
publishDate 2008
dc.date.none.fl_str_mv 2008
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1523/JNEUROSCI.1915-08.2008
http://hdl.handle.net/10459.1/56688
url https://doi.org/10.1523/JNEUROSCI.1915-08.2008
http://hdl.handle.net/10459.1/56688
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv MIECI/PN2004-2007/SAF2007-60287
MIECI/PN2004-2007/SAF2005-0171
Reproducció del document publicat a https://doi.org/10.1523/JNEUROSCI.1915-08.2008
The Journal of Neuroscience, 2008, vol. 28, núm. 48, p. 12700-12712
dc.rights.none.fl_str_mv (c) Society for Neuroscience, 2008
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Society for Neuroscience, 2008
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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