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dc.contributor.authorJimeno, David-
dc.contributor.authorGómez, Carmela-
dc.contributor.authorCalzada, Nuria-
dc.contributor.authorVilla, Pedro de la-
dc.contributor.authorLillo, Concepción-
dc.contributor.authorSantos de Dios, Eugenio-
dc.date.accessioned2018-08-14T10:03:51Z-
dc.date.available2018-08-14T10:03:51Z-
dc.date.issued2016-
dc.identifierdoi: 10.1242/jcs.180919-
dc.identifierissn: 0021-9533-
dc.identifiere-issn: 1477-9137-
dc.identifier.citationJournal of Cell Science 129(4): 729-742 (2016)-
dc.identifier.urihttp://hdl.handle.net/10261/168694-
dc.description.abstractDetailed immunocytochemical analyses comparing wild-type (WT), GRF1-knockout (KO), GRF2-KO and GRF1/2 double-knockout (DKO) mouse retinas uncovered the specific accumulation of misplaced, 'ectopic' cone photoreceptor nuclei in the photoreceptor segment (PS) area of retinas from GRF2-KO and GRF1/2-DKO, but not of WT or GRF1-KO mice. Localization of ectopic nuclei in the PS area of GRF2-depleted retinas occurred postnatally and peaked between postnatal day (P)11 and P15. Mechanistically, the generation of this phenotype involved disruption of the outer limiting membrane and intrusion into the PS layer by cone nuclei displaying significant perinuclear accumulation of signaling molecules known to participate in nuclear migration and cytoskeletal reorganization, such as PAR3, PAR6 and activated, phosphorylated forms of PAK, MLC2 and VASP. Electroretinographic recordings showed specific impairment of cone-mediated retinal function in GRF2-KO and GRF1/2-DKO retinas compared with WT controls. These data identify defective cone nuclear migration as a novel phenotype in mouse retinas lacking GRF2 and support a crucial role of GRF2 in control of the nuclear migration processes required for proper postnatal development and function of retinal cone photoreceptors.-
dc.description.sponsorshipWork was supported by the Instituto de Salud Carlos III (ISCIII, MINECO) [FIS PI13/02846 and PI3/02098, RTICC RD12/0036/0001]; Junta de Castilla y León (JCyL), Spain [SA181U13 and BIO/SA03/14]; and the Fundación Lucha contra la Ceguera (FUNDALUCE). D.J. and C.G. were supported by Red Temática de Investigación Cooperativa en Cáncer (RTICC) and Asociación Española Contra el Cáncer (AECC), respectively.-
dc.publisherCompany of Biologists-
dc.relation.isversionofPublisher's version-
dc.rightsopenAccess-
dc.subjectNuclear migration-
dc.subjectCone photoreceptor-
dc.subjectGRF2-
dc.subjectRas signaling-
dc.subjectGEF-
dc.subjectGRF1-
dc.subjectIntracellular traffic-
dc.subjectRetina-
dc.titleRasGRF2 controls nuclear migration in postnatal retinal cone photoreceptors-
dc.typeartículo-
dc.relation.publisherversionhttps://doi.org/10.1242/jcs.180919-
dc.date.updated2018-08-14T10:03:52Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.contributor.funderAsociación Española Contra el Cáncer-
dc.contributor.funderRed Temática de Investigación Cooperativa en Cáncer (España)-
dc.contributor.funderFundación Lucha contra la Ceguera-
dc.contributor.funderMinisterio de Economía y Competitividad (España)-
dc.contributor.funderInstituto de Salud Carlos III-
dc.contributor.funderJunta de Castilla y León-
dc.relation.csic-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
dc.identifier.pmid26743081-
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