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dc.contributor.authorJavier-Torrent, Míriam
dc.contributor.authorMarco, Sergio
dc.contributor.authorRocandio, Daniel
dc.contributor.authorPons-Vizcarra, Maria
dc.contributor.authorJanes, Peter W
dc.contributor.authorLackmann, Martin
dc.contributor.authorEgea Navarro, Joaquim
dc.contributor.authorSaura, Carlos A
dc.date.accessioned2020-03-12T12:34:54Z
dc.date.available2020-03-12T12:34:54Z
dc.date.issued2019
dc.identifier.issn2050-084X
dc.identifier.urihttp://hdl.handle.net/10459.1/68213
dc.description.abstractEphA/ephrin signaling regulates axon growth and guidance of neurons, but whether this process occurs also independently of ephrins is unclear. We show that presenilin-1 (PS1)/γ-secretase is required for axon growth in the developing mouse brain. PS1/γ-secretase mediates axon growth by inhibiting RhoA signaling and cleaving EphA3 independently of ligand to generate an intracellular domain (ICD) fragment that reverses axon defects in PS1/γ-secretase- and EphA3-deficient hippocampal neurons. Proteomic analysis revealed that EphA3 ICD binds to non-muscle myosin IIA (NMIIA) and increases its phosphorylation (Ser1943), which promotes NMIIA filament disassembly and cytoskeleton rearrangement. PS1/γ-secretase-deficient neurons show decreased phosphorylated NMIIA and NMIIA/actin colocalization. Moreover, pharmacological NMII inhibition reverses axon retraction in PS-deficient neurons suggesting that NMIIA mediates PS/EphA3-dependent axon elongation. In conclusion, PS/γ-secretase-dependent EphA3 cleavage mediates axon growth by regulating filament assembly through RhoA signaling and NMIIA, suggesting opposite roles of EphA3 on inhibiting (ligand-dependent) and promoting (receptor processing) axon growth in developing neurons.ca_ES
dc.description.sponsorshipMinisterio de Economia y Competitividad SAF2013-43900-R Carlos A Saura, Ministerio de Economia y Competitividad SAF2016-80027-R Carlos A Saura, Ministerio de Economia y Competitividad CIBERNED CB06/05/0042 Carlos A Saura Generalitat de Catalunya ICREA Academia Carlos A Saura, Generalitat de Catalunya 2017 SGR749 Carlos A Saura.ca_ES
dc.language.isoengca_ES
dc.publishereLife Sciences Publicationsca_ES
dc.relationMINECO/PN2013-2016/SAF2013-43900-Rca_ES
dc.relationMINECO/PN2013-2016/SAF2016-80027-Rca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.7554/eLife.43646ca_ES
dc.relation.ispartofeLife, 2019, vol. 8ca_ES
dc.rightscc-by, (c) Javier-Torrent et al., 2019ca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.otherNeurociènciesca_ES
dc.subject.otherNeuronesca_ES
dc.subject.otherAxonsca_ES
dc.titlePresenilin/γ-secretase-dependent EphA3 processing mediates axon elongation through non-muscle myosin IIAca_ES
dc.title.alternativePresenilin/gamma-secretase-dependent EphA3 processing mediates axon elongation through non-muscle myosin IIAca_ES
dc.typeinfo:eu-repo/semantics/articleca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.identifier.doihttps://doi.org/10.7554/eLife.43646


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cc-by, (c) Javier-Torrent et al., 2019
Except where otherwise noted, this item's license is described as cc-by, (c) Javier-Torrent et al., 2019