ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons

Autores
Song, Wenyu; Lapid de Volosin, Marta Edith; Cragnolini, Andrea Beatriz; Hempstead, Barbara L.; Friedman, Wilma J.
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Proneurotrophins and mature neurotrophins activate different signaling pathways with distinct effects on their target cells: proneurotrophins can induce apoptotic signaling via p75NTR, whereas mature neurotrophins activate Trk receptors to influence survival and differentiation. Here, we demonstrate that the PTEN (phosphatase and tensin homolog deleted on chromosome 10) phosphatase represents a novel switch between the survival and apoptotic signaling pathways in rat CNS neurons. Simultaneous activation of p75 NTR by proNGF and TrkB signaling by BDNF elicited apoptosis despite TrkB phosphorylation. Apoptosis induced by p75NTR required suppression of TrkB-induced phosphoinositide-3 kinase signaling, mediated by induction of PTEN, for apoptosis to proceed. Inhibition of PTEN restored the ability of BDNF to phosphorylate Akt and protect cultured basal forebrain neurons from proNGF-induced death. In vivo, inhibition or knockdown of PTEN after pilocarpine-induced seizures protected CNS neurons from p75 NTR-mediated death, demonstrating that PTEN is a crucial factor mediating the balance between p75NTR-induced apoptotic signaling and Trk-mediated survival signaling in brain neurons.
Fil: Song, Wenyu. Rutgers University. School of Engineering. Chemical and Biochemical Engineering Department; Estados Unidos
Fil: Lapid de Volosin, Marta Edith. Rutgers University. School of Engineering. Chemical and Biochemical Engineering Department; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Cragnolini, Andrea Beatriz. Rutgers University. School of Engineering. Chemical and Biochemical Engineering Department; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Hempstead, Barbara L.. Cornell University; Estados Unidos
Fil: Friedman, Wilma J.. Rutgers University. School of Engineering. Chemical and Biochemical Engineering Department; Estados Unidos
Materia
ProNGF
P75NTR
PTEN
Neuronal death
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/188983
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neuronsSong, WenyuLapid de Volosin, Marta EdithCragnolini, Andrea BeatrizHempstead, Barbara L.Friedman, Wilma J.ProNGFP75NTRPTENNeuronal deathhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Proneurotrophins and mature neurotrophins activate different signaling pathways with distinct effects on their target cells: proneurotrophins can induce apoptotic signaling via p75NTR, whereas mature neurotrophins activate Trk receptors to influence survival and differentiation. Here, we demonstrate that the PTEN (phosphatase and tensin homolog deleted on chromosome 10) phosphatase represents a novel switch between the survival and apoptotic signaling pathways in rat CNS neurons. Simultaneous activation of p75 NTR by proNGF and TrkB signaling by BDNF elicited apoptosis despite TrkB phosphorylation. Apoptosis induced by p75NTR required suppression of TrkB-induced phosphoinositide-3 kinase signaling, mediated by induction of PTEN, for apoptosis to proceed. Inhibition of PTEN restored the ability of BDNF to phosphorylate Akt and protect cultured basal forebrain neurons from proNGF-induced death. In vivo, inhibition or knockdown of PTEN after pilocarpine-induced seizures protected CNS neurons from p75 NTR-mediated death, demonstrating that PTEN is a crucial factor mediating the balance between p75NTR-induced apoptotic signaling and Trk-mediated survival signaling in brain neurons.Fil: Song, Wenyu. Rutgers University. School of Engineering. Chemical and Biochemical Engineering Department; Estados UnidosFil: Lapid de Volosin, Marta Edith. Rutgers University. School of Engineering. Chemical and Biochemical Engineering Department; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Cragnolini, Andrea Beatriz. Rutgers University. School of Engineering. Chemical and Biochemical Engineering Department; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Hempstead, Barbara L.. Cornell University; Estados UnidosFil: Friedman, Wilma J.. Rutgers University. School of Engineering. Chemical and Biochemical Engineering Department; Estados UnidosSociety for Neuroscience2010-11-17info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/188983Song, Wenyu; Lapid de Volosin, Marta Edith; Cragnolini, Andrea Beatriz; Hempstead, Barbara L.; Friedman, Wilma J.; ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons; Society for Neuroscience; Journal of Neuroscience; 30; 46; 17-11-2010; 15608-156150270-64741529-2401CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/30/46/15608info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.2581-10.2010info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:29:32Zoai:ri.conicet.gov.ar:11336/188983instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:29:33.081CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons
title ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons
spellingShingle ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons
Song, Wenyu
ProNGF
P75NTR
PTEN
Neuronal death
title_short ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons
title_full ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons
title_fullStr ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons
title_full_unstemmed ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons
title_sort ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons
dc.creator.none.fl_str_mv Song, Wenyu
Lapid de Volosin, Marta Edith
Cragnolini, Andrea Beatriz
Hempstead, Barbara L.
Friedman, Wilma J.
author Song, Wenyu
author_facet Song, Wenyu
Lapid de Volosin, Marta Edith
Cragnolini, Andrea Beatriz
Hempstead, Barbara L.
Friedman, Wilma J.
author_role author
author2 Lapid de Volosin, Marta Edith
Cragnolini, Andrea Beatriz
Hempstead, Barbara L.
Friedman, Wilma J.
author2_role author
author
author
author
dc.subject.none.fl_str_mv ProNGF
P75NTR
PTEN
Neuronal death
topic ProNGF
P75NTR
PTEN
Neuronal death
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Proneurotrophins and mature neurotrophins activate different signaling pathways with distinct effects on their target cells: proneurotrophins can induce apoptotic signaling via p75NTR, whereas mature neurotrophins activate Trk receptors to influence survival and differentiation. Here, we demonstrate that the PTEN (phosphatase and tensin homolog deleted on chromosome 10) phosphatase represents a novel switch between the survival and apoptotic signaling pathways in rat CNS neurons. Simultaneous activation of p75 NTR by proNGF and TrkB signaling by BDNF elicited apoptosis despite TrkB phosphorylation. Apoptosis induced by p75NTR required suppression of TrkB-induced phosphoinositide-3 kinase signaling, mediated by induction of PTEN, for apoptosis to proceed. Inhibition of PTEN restored the ability of BDNF to phosphorylate Akt and protect cultured basal forebrain neurons from proNGF-induced death. In vivo, inhibition or knockdown of PTEN after pilocarpine-induced seizures protected CNS neurons from p75 NTR-mediated death, demonstrating that PTEN is a crucial factor mediating the balance between p75NTR-induced apoptotic signaling and Trk-mediated survival signaling in brain neurons.
Fil: Song, Wenyu. Rutgers University. School of Engineering. Chemical and Biochemical Engineering Department; Estados Unidos
Fil: Lapid de Volosin, Marta Edith. Rutgers University. School of Engineering. Chemical and Biochemical Engineering Department; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Cragnolini, Andrea Beatriz. Rutgers University. School of Engineering. Chemical and Biochemical Engineering Department; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Hempstead, Barbara L.. Cornell University; Estados Unidos
Fil: Friedman, Wilma J.. Rutgers University. School of Engineering. Chemical and Biochemical Engineering Department; Estados Unidos
description Proneurotrophins and mature neurotrophins activate different signaling pathways with distinct effects on their target cells: proneurotrophins can induce apoptotic signaling via p75NTR, whereas mature neurotrophins activate Trk receptors to influence survival and differentiation. Here, we demonstrate that the PTEN (phosphatase and tensin homolog deleted on chromosome 10) phosphatase represents a novel switch between the survival and apoptotic signaling pathways in rat CNS neurons. Simultaneous activation of p75 NTR by proNGF and TrkB signaling by BDNF elicited apoptosis despite TrkB phosphorylation. Apoptosis induced by p75NTR required suppression of TrkB-induced phosphoinositide-3 kinase signaling, mediated by induction of PTEN, for apoptosis to proceed. Inhibition of PTEN restored the ability of BDNF to phosphorylate Akt and protect cultured basal forebrain neurons from proNGF-induced death. In vivo, inhibition or knockdown of PTEN after pilocarpine-induced seizures protected CNS neurons from p75 NTR-mediated death, demonstrating that PTEN is a crucial factor mediating the balance between p75NTR-induced apoptotic signaling and Trk-mediated survival signaling in brain neurons.
publishDate 2010
dc.date.none.fl_str_mv 2010-11-17
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/188983
Song, Wenyu; Lapid de Volosin, Marta Edith; Cragnolini, Andrea Beatriz; Hempstead, Barbara L.; Friedman, Wilma J.; ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons; Society for Neuroscience; Journal of Neuroscience; 30; 46; 17-11-2010; 15608-15615
0270-6474
1529-2401
CONICET Digital
CONICET
url http://hdl.handle.net/11336/188983
identifier_str_mv Song, Wenyu; Lapid de Volosin, Marta Edith; Cragnolini, Andrea Beatriz; Hempstead, Barbara L.; Friedman, Wilma J.; ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons; Society for Neuroscience; Journal of Neuroscience; 30; 46; 17-11-2010; 15608-15615
0270-6474
1529-2401
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/30/46/15608
info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.2581-10.2010
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846082767176073216
score 13.22299

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