FLRT3 Is a Robo1-Interacting Protein that Determines Netrin-1 Attraction in Developing Axons

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dc.contributor.authorLeyva-Díaz, Eduardo
dc.contributor.authorToro, Daniel del
dc.contributor.authorMenal Castellote, Maria José
dc.contributor.authorCambray Carner, Serafí
dc.contributor.authorSusín, Rafael
dc.contributor.authorTessier-Lavigne, Marc
dc.contributor.authorKlein, Rüdiger
dc.contributor.authorEgea Navarro, Joaquim
dc.contributor.authorLópez-Bendito, Guillermina
dc.date.accessioned2016-04-18T08:35:20Z
dc.date.embargoEndDate2025-01-01
dc.date.issued2014
dc.description.abstractBackground: Guidance molecules are normally presented to cells in an overlapping fashion; however, little is known about how their signals are integrated to control the formation of neural circuits. In the thalamocortical system, the topographical sorting of distinct axonal subpopulations relies on the emergent cooperation between Slit1 and Netrin-1 guidance cues presented by intermediate cellular targets. However, the mechanism by which both cues interact to drive distinct axonal responses remains unknown. Results: Here, we show that the attractive response to the guidance cue Netrin-1 is controlled by Slit/Robo1 signaling and by FLRT3, a novel coreceptor for Robo1. While thalamic axons lacking FLRT3 are insensitive to Netrin-1, thalamic axons containing FLRT3 can modulate their Netrin-1 responsiveness in a context-dependent manner. In the presence of Slit1, both Robo1 and FLRT3 receptors are required to induce Netrin-1 attraction by the upregulation of surface DCC through the activation of protein kinase A. Finally, the absence of FLRT3 produces defects in axon guidance in vivo. Conclusions: These results highlight a novel mechanism by which interactions between limited numbers of axon guidance cues can multiply the responses in developing axons, as required for proper axonal tract formation in the mammalian brain.ca_ES
dc.description.sponsorshipThis work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB870 to R.K.), the Spanish MICINN (BFU2010-18055 to J.E. and BFU2012-34298 to G.L.-B.), FP7-PEOPLE-2011-CIG (PCIG9-GA-2011- 293980 to J.E.), the CONSOLIDER programme CSD2007-00023, and an ERC grant (ERC-2009-StG_20081210 to G.L.-B.). J.E. is a Ramón y Cajal investigator (RYC-2008-03342). G.L.-B. is an EMBO Young Investigator.ca_ES
dc.identifier.doihttps://doi.org/10.1016/j.cub.2014.01.042
dc.identifier.idgrec021253
dc.identifier.issn0960-9822
dc.identifier.urihttp://hdl.handle.net/10459.1/56846
dc.language.isoengca_ES
dc.publisherElsevierca_ES
dc.relationMICINN/PN2008-2011/BFU2010-18055
dc.relationMICINN/PN2008-2011/BFU2012-34298
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1016/j.cub.2014.01.042ca_ES
dc.relation.ispartofCurrent Biology, 2014, vol. 24, núm. 5, p. 494-508ca_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/293980
dc.rights(c) Elsevier Ltd., 2014ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.titleFLRT3 Is a Robo1-Interacting Protein that Determines Netrin-1 Attraction in Developing Axonsca_ES
dc.typearticleca_ES
dc.type.versionpublishedVersionca_ES
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