ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1

Autores
Pasten, Consuelo; Cerda, Joaquín; Jausoro, Ignacio; Court, Felipe A.; Caceres, Alfredo Oscar; Marzolo, Maria Paz
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
ApoER2 and its ligand Reelin participate in neuronal migration during development. Upon receptor binding, Reelin induces the proteolytic processing of ApoER2 as well as the activation of signaling pathway, including small Rho GTPases. Besides its presence in the central nervous system (CNS), Reelin is also secreted by Schwann cells (SCs), the glial cells of the peripheral nervous system (PNS). Reelin deficient mice (reeler) show decreased axonal regeneration in the PNS; however neither the presence of ApoER2 nor the role of the Reelin signaling pathway in the PNS have been evaluated. Interestingly SC migration occurs during PNS development and during injury-induced regeneration and involves activation of small Rho GTPases. Thus, Reelin-ApoER2 might regulate SC migration during axon regeneration in the PNS. Here we demonstrate the presence of ApoER2 in PNS. After sciatic nerve injury Reelin was induced and its receptor ApoER2 was proteolytically processed. In vitro, SCs express both Reelin and ApoER2 and Reelin induces SC migration. To elucidate the molecular mechanism underlying Reelin-dependent SC migration, we examined the involvement of Rac1, a conspicuous small GTPase family member. FRET experiments revealed that Reelin activates Rac1 at the leading edge of SCs. In addition, Tiam1, a major Rac1-specific GEF was required for Reelin-induced SC migration. Moreover, Reelin-induced SC migration was decreased after suppression of the polarity protein PAR3, consistent with its association to Tiam1. Even more interesting, we demonstrated that PAR3 binds preferentially to the full-length cytoplasmic tail of ApoER2 corresponding to the splice-variant containing the exon 19 that encodes a proline-rich insert and that ApoER2 was required for SC migration. Our study reveals a novel function for Reelin/ApoER2 in PNS, inducing cell migration of SCs, a process relevant for PNS development and regeneration.
Fil: Pasten, Consuelo. Pontificia Universidad Católica de Chile; Chile. Millennium Nucleus for Regenerative Biology; Chile
Fil: Cerda, Joaquín. Pontificia Universidad Católica de Chile; Chile. Millennium Nucleus for Regenerative Biology; Chile
Fil: Jausoro, Ignacio. Pontificia Universidad Católica de Chile; Chile. Millennium Nucleus for Regenerative Biology; Chile
Fil: Court, Felipe A.. Pontificia Universidad Católica de Chile; Chile. Millennium Nucleus for Regenerative Biology; Chile
Fil: Caceres, Alfredo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Marzolo, Maria Paz. Millennium Nucleus for Regenerative Biology; Chile. Pontificia Universidad Católica de Chile; Chile
Materia
Apoer2
Migration
Par3
Proteolytic Processing
Reelin
Rho Gtpases
Schwann Cells
Sciatic Nerve
Tiam1
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/37914
Acceder
id CONICETDig_27af0bbc0559a869c17742b5a4cb943d
oai_identifier_str oai:ri.conicet.gov.ar:11336/37914
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1Pasten, ConsueloCerda, JoaquínJausoro, IgnacioCourt, Felipe A.Caceres, Alfredo OscarMarzolo, Maria PazApoer2MigrationPar3Proteolytic ProcessingReelinRho GtpasesSchwann CellsSciatic NerveTiam1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3ApoER2 and its ligand Reelin participate in neuronal migration during development. Upon receptor binding, Reelin induces the proteolytic processing of ApoER2 as well as the activation of signaling pathway, including small Rho GTPases. Besides its presence in the central nervous system (CNS), Reelin is also secreted by Schwann cells (SCs), the glial cells of the peripheral nervous system (PNS). Reelin deficient mice (reeler) show decreased axonal regeneration in the PNS; however neither the presence of ApoER2 nor the role of the Reelin signaling pathway in the PNS have been evaluated. Interestingly SC migration occurs during PNS development and during injury-induced regeneration and involves activation of small Rho GTPases. Thus, Reelin-ApoER2 might regulate SC migration during axon regeneration in the PNS. Here we demonstrate the presence of ApoER2 in PNS. After sciatic nerve injury Reelin was induced and its receptor ApoER2 was proteolytically processed. In vitro, SCs express both Reelin and ApoER2 and Reelin induces SC migration. To elucidate the molecular mechanism underlying Reelin-dependent SC migration, we examined the involvement of Rac1, a conspicuous small GTPase family member. FRET experiments revealed that Reelin activates Rac1 at the leading edge of SCs. In addition, Tiam1, a major Rac1-specific GEF was required for Reelin-induced SC migration. Moreover, Reelin-induced SC migration was decreased after suppression of the polarity protein PAR3, consistent with its association to Tiam1. Even more interesting, we demonstrated that PAR3 binds preferentially to the full-length cytoplasmic tail of ApoER2 corresponding to the splice-variant containing the exon 19 that encodes a proline-rich insert and that ApoER2 was required for SC migration. Our study reveals a novel function for Reelin/ApoER2 in PNS, inducing cell migration of SCs, a process relevant for PNS development and regeneration.Fil: Pasten, Consuelo. Pontificia Universidad Católica de Chile; Chile. Millennium Nucleus for Regenerative Biology; ChileFil: Cerda, Joaquín. Pontificia Universidad Católica de Chile; Chile. Millennium Nucleus for Regenerative Biology; ChileFil: Jausoro, Ignacio. Pontificia Universidad Católica de Chile; Chile. Millennium Nucleus for Regenerative Biology; ChileFil: Court, Felipe A.. Pontificia Universidad Católica de Chile; Chile. Millennium Nucleus for Regenerative Biology; ChileFil: Caceres, Alfredo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Marzolo, Maria Paz. Millennium Nucleus for Regenerative Biology; Chile. Pontificia Universidad Católica de Chile; ChileAcademic Press Inc Elsevier Science2015-11info: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/11336/37914Pasten, Consuelo; Cerda, Joaquín; Jausoro, Ignacio; Court, Felipe A.; Caceres, Alfredo Oscar; et al.; ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1; Academic Press Inc Elsevier Science; Molecular and Cellular Neuroscience; 69; 11-2015; 1-111044-7431CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.mcn.2015.09.004info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1044743115300221info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:07:06Zoai:ri.conicet.gov.ar:11336/37914instacron: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:34982025-09-03 10:07:07.262CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1
title ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1
spellingShingle ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1
Pasten, Consuelo
Apoer2
Migration
Par3
Proteolytic Processing
Reelin
Rho Gtpases
Schwann Cells
Sciatic Nerve
Tiam1
title_short ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1
title_full ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1
title_fullStr ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1
title_full_unstemmed ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1
title_sort ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1
dc.creator.none.fl_str_mv Pasten, Consuelo
Cerda, Joaquín
Jausoro, Ignacio
Court, Felipe A.
Caceres, Alfredo Oscar
Marzolo, Maria Paz
author Pasten, Consuelo
author_facet Pasten, Consuelo
Cerda, Joaquín
Jausoro, Ignacio
Court, Felipe A.
Caceres, Alfredo Oscar
Marzolo, Maria Paz
author_role author
author2 Cerda, Joaquín
Jausoro, Ignacio
Court, Felipe A.
Caceres, Alfredo Oscar
Marzolo, Maria Paz
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Apoer2
Migration
Par3
Proteolytic Processing
Reelin
Rho Gtpases
Schwann Cells
Sciatic Nerve
Tiam1
topic Apoer2
Migration
Par3
Proteolytic Processing
Reelin
Rho Gtpases
Schwann Cells
Sciatic Nerve
Tiam1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv ApoER2 and its ligand Reelin participate in neuronal migration during development. Upon receptor binding, Reelin induces the proteolytic processing of ApoER2 as well as the activation of signaling pathway, including small Rho GTPases. Besides its presence in the central nervous system (CNS), Reelin is also secreted by Schwann cells (SCs), the glial cells of the peripheral nervous system (PNS). Reelin deficient mice (reeler) show decreased axonal regeneration in the PNS; however neither the presence of ApoER2 nor the role of the Reelin signaling pathway in the PNS have been evaluated. Interestingly SC migration occurs during PNS development and during injury-induced regeneration and involves activation of small Rho GTPases. Thus, Reelin-ApoER2 might regulate SC migration during axon regeneration in the PNS. Here we demonstrate the presence of ApoER2 in PNS. After sciatic nerve injury Reelin was induced and its receptor ApoER2 was proteolytically processed. In vitro, SCs express both Reelin and ApoER2 and Reelin induces SC migration. To elucidate the molecular mechanism underlying Reelin-dependent SC migration, we examined the involvement of Rac1, a conspicuous small GTPase family member. FRET experiments revealed that Reelin activates Rac1 at the leading edge of SCs. In addition, Tiam1, a major Rac1-specific GEF was required for Reelin-induced SC migration. Moreover, Reelin-induced SC migration was decreased after suppression of the polarity protein PAR3, consistent with its association to Tiam1. Even more interesting, we demonstrated that PAR3 binds preferentially to the full-length cytoplasmic tail of ApoER2 corresponding to the splice-variant containing the exon 19 that encodes a proline-rich insert and that ApoER2 was required for SC migration. Our study reveals a novel function for Reelin/ApoER2 in PNS, inducing cell migration of SCs, a process relevant for PNS development and regeneration.
Fil: Pasten, Consuelo. Pontificia Universidad Católica de Chile; Chile. Millennium Nucleus for Regenerative Biology; Chile
Fil: Cerda, Joaquín. Pontificia Universidad Católica de Chile; Chile. Millennium Nucleus for Regenerative Biology; Chile
Fil: Jausoro, Ignacio. Pontificia Universidad Católica de Chile; Chile. Millennium Nucleus for Regenerative Biology; Chile
Fil: Court, Felipe A.. Pontificia Universidad Católica de Chile; Chile. Millennium Nucleus for Regenerative Biology; Chile
Fil: Caceres, Alfredo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Marzolo, Maria Paz. Millennium Nucleus for Regenerative Biology; Chile. Pontificia Universidad Católica de Chile; Chile
description ApoER2 and its ligand Reelin participate in neuronal migration during development. Upon receptor binding, Reelin induces the proteolytic processing of ApoER2 as well as the activation of signaling pathway, including small Rho GTPases. Besides its presence in the central nervous system (CNS), Reelin is also secreted by Schwann cells (SCs), the glial cells of the peripheral nervous system (PNS). Reelin deficient mice (reeler) show decreased axonal regeneration in the PNS; however neither the presence of ApoER2 nor the role of the Reelin signaling pathway in the PNS have been evaluated. Interestingly SC migration occurs during PNS development and during injury-induced regeneration and involves activation of small Rho GTPases. Thus, Reelin-ApoER2 might regulate SC migration during axon regeneration in the PNS. Here we demonstrate the presence of ApoER2 in PNS. After sciatic nerve injury Reelin was induced and its receptor ApoER2 was proteolytically processed. In vitro, SCs express both Reelin and ApoER2 and Reelin induces SC migration. To elucidate the molecular mechanism underlying Reelin-dependent SC migration, we examined the involvement of Rac1, a conspicuous small GTPase family member. FRET experiments revealed that Reelin activates Rac1 at the leading edge of SCs. In addition, Tiam1, a major Rac1-specific GEF was required for Reelin-induced SC migration. Moreover, Reelin-induced SC migration was decreased after suppression of the polarity protein PAR3, consistent with its association to Tiam1. Even more interesting, we demonstrated that PAR3 binds preferentially to the full-length cytoplasmic tail of ApoER2 corresponding to the splice-variant containing the exon 19 that encodes a proline-rich insert and that ApoER2 was required for SC migration. Our study reveals a novel function for Reelin/ApoER2 in PNS, inducing cell migration of SCs, a process relevant for PNS development and regeneration.
publishDate 2015
dc.date.none.fl_str_mv 2015-11
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/11336/37914
Pasten, Consuelo; Cerda, Joaquín; Jausoro, Ignacio; Court, Felipe A.; Caceres, Alfredo Oscar; et al.; ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1; Academic Press Inc Elsevier Science; Molecular and Cellular Neuroscience; 69; 11-2015; 1-11
1044-7431
CONICET Digital
CONICET
url http://hdl.handle.net/11336/37914
identifier_str_mv Pasten, Consuelo; Cerda, Joaquín; Jausoro, Ignacio; Court, Felipe A.; Caceres, Alfredo Oscar; et al.; ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1; Academic Press Inc Elsevier Science; Molecular and Cellular Neuroscience; 69; 11-2015; 1-11
1044-7431
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mcn.2015.09.004
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1044743115300221
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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
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score 13.13397

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