Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development

Autores
Rozés Salvador, María Victoria; Wilson Rodriguez, Carlos; Olmos, Cristina; Gonzalez Billault, Christian; Conde, Cecilia Beatriz
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Neural development is a complex process that involves critical events, including cytoskeleton dynamics and selective trafficking of proteins to defined cellular destinations. In this regard, Smad Anchor for Receptor Activation (SARA) is an early endosome resident protein, where perform trafficking- associated functions. In addition, SARA is also involved in cell signaling, including the TGFβ-dependent pathway. Accordingly, SARA, and TGFβ signaling are required for proper axonal specification and migration of cortical neurons, unveiling a critical role for neuronal development. However, the cooperative action between the TGFβ pathway and SARA to this process has remained understudied. In this work, we show novel evidence suggesting a cross-talk between SARA and TGFβ pathway needed for proper polarization, axonal specification, growth and cortical migration of central neurons both in vitro and in vivo. Using microscopy tools and cultured hippocampal neurons, we show a local interaction between SARA and TβRI (TGFβ I receptor) at endosomes. In addition, SARA loss of function, induced by the expression of the dominant-negative SARA-F728A, over-activates the TGFβ pathway, most likely by preserving phosphorylated TβRI. Consequently, SARA-mediated activation of TGFβ pathway impacts on neuronal development, promoting axonal growth and cortical migration of neurons during brain development. Moreover, our data suggests that SARA basally prevents the activation of TβRI through the recruitment of the inhibitory complex PP1c/GADD34 in polarizing neurons. Together, these results propose that SARA is a negative regulator of the TGFβ pathway, being critical for a proper orchestration for neuronal development.
Fil: Rozés Salvador, María Victoria. Universidad Nacional de Villa María. Instituto Académico Pedagógico de Ciencias Básicas y Aplicadas; Argentina. 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: Wilson Rodriguez, Carlos. 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. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina
Fil: Olmos, Cristina. Universidad de Chile; Chile
Fil: Gonzalez Billault, Christian. Universidad de Chile; Chile
Fil: Conde, Cecilia Beatriz. 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
Materia
AXON
DEVELOPMENT
ENDOSOMES
MIGRATION
NEURONS
SMAD ANCHOR FOR RECEPTOR ACTIVATION (SARA)
TGFΒ
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:11336/140206
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/140206
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal DevelopmentRozés Salvador, María VictoriaWilson Rodriguez, CarlosOlmos, CristinaGonzalez Billault, ChristianConde, Cecilia BeatrizAXONDEVELOPMENTENDOSOMESMIGRATIONNEURONSSMAD ANCHOR FOR RECEPTOR ACTIVATION (SARA)TGFΒhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Neural development is a complex process that involves critical events, including cytoskeleton dynamics and selective trafficking of proteins to defined cellular destinations. In this regard, Smad Anchor for Receptor Activation (SARA) is an early endosome resident protein, where perform trafficking- associated functions. In addition, SARA is also involved in cell signaling, including the TGFβ-dependent pathway. Accordingly, SARA, and TGFβ signaling are required for proper axonal specification and migration of cortical neurons, unveiling a critical role for neuronal development. However, the cooperative action between the TGFβ pathway and SARA to this process has remained understudied. In this work, we show novel evidence suggesting a cross-talk between SARA and TGFβ pathway needed for proper polarization, axonal specification, growth and cortical migration of central neurons both in vitro and in vivo. Using microscopy tools and cultured hippocampal neurons, we show a local interaction between SARA and TβRI (TGFβ I receptor) at endosomes. In addition, SARA loss of function, induced by the expression of the dominant-negative SARA-F728A, over-activates the TGFβ pathway, most likely by preserving phosphorylated TβRI. Consequently, SARA-mediated activation of TGFβ pathway impacts on neuronal development, promoting axonal growth and cortical migration of neurons during brain development. Moreover, our data suggests that SARA basally prevents the activation of TβRI through the recruitment of the inhibitory complex PP1c/GADD34 in polarizing neurons. Together, these results propose that SARA is a negative regulator of the TGFβ pathway, being critical for a proper orchestration for neuronal development.Fil: Rozés Salvador, María Victoria. Universidad Nacional de Villa María. Instituto Académico Pedagógico de Ciencias Básicas y Aplicadas; Argentina. 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: Wilson Rodriguez, Carlos. 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. Instituto Universitario de Ciencias Biomédicas de Córdoba; ArgentinaFil: Olmos, Cristina. Universidad de Chile; ChileFil: Gonzalez Billault, Christian. Universidad de Chile; ChileFil: Conde, Cecilia Beatriz. 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; ArgentinaFrontiers Media S.A.2020-09info: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/11336/140206Rozés Salvador, María Victoria; Wilson Rodriguez, Carlos; Olmos, Cristina; Gonzalez Billault, Christian; Conde, Cecilia Beatriz; Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development; Frontiers Media S.A.; Frontiers in Cell and Developmental Biology; 8; 9-2020; 1-132296-634XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fcell.2020.550267info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:14:46Zoai:ri.conicet.gov.ar:11336/140206instacron: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 15:14:46.318CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development
title Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development
spellingShingle Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development
Rozés Salvador, María Victoria
AXON
DEVELOPMENT
ENDOSOMES
MIGRATION
NEURONS
SMAD ANCHOR FOR RECEPTOR ACTIVATION (SARA)
TGFΒ
title_short Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development
title_full Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development
title_fullStr Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development
title_full_unstemmed Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development
title_sort Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development
dc.creator.none.fl_str_mv Rozés Salvador, María Victoria
Wilson Rodriguez, Carlos
Olmos, Cristina
Gonzalez Billault, Christian
Conde, Cecilia Beatriz
author Rozés Salvador, María Victoria
author_facet Rozés Salvador, María Victoria
Wilson Rodriguez, Carlos
Olmos, Cristina
Gonzalez Billault, Christian
Conde, Cecilia Beatriz
author_role author
author2 Wilson Rodriguez, Carlos
Olmos, Cristina
Gonzalez Billault, Christian
Conde, Cecilia Beatriz
author2_role author
author
author
author
dc.subject.none.fl_str_mv AXON
DEVELOPMENT
ENDOSOMES
MIGRATION
NEURONS
SMAD ANCHOR FOR RECEPTOR ACTIVATION (SARA)
TGFΒ
topic AXON
DEVELOPMENT
ENDOSOMES
MIGRATION
NEURONS
SMAD ANCHOR FOR RECEPTOR ACTIVATION (SARA)
TGFΒ
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Neural development is a complex process that involves critical events, including cytoskeleton dynamics and selective trafficking of proteins to defined cellular destinations. In this regard, Smad Anchor for Receptor Activation (SARA) is an early endosome resident protein, where perform trafficking- associated functions. In addition, SARA is also involved in cell signaling, including the TGFβ-dependent pathway. Accordingly, SARA, and TGFβ signaling are required for proper axonal specification and migration of cortical neurons, unveiling a critical role for neuronal development. However, the cooperative action between the TGFβ pathway and SARA to this process has remained understudied. In this work, we show novel evidence suggesting a cross-talk between SARA and TGFβ pathway needed for proper polarization, axonal specification, growth and cortical migration of central neurons both in vitro and in vivo. Using microscopy tools and cultured hippocampal neurons, we show a local interaction between SARA and TβRI (TGFβ I receptor) at endosomes. In addition, SARA loss of function, induced by the expression of the dominant-negative SARA-F728A, over-activates the TGFβ pathway, most likely by preserving phosphorylated TβRI. Consequently, SARA-mediated activation of TGFβ pathway impacts on neuronal development, promoting axonal growth and cortical migration of neurons during brain development. Moreover, our data suggests that SARA basally prevents the activation of TβRI through the recruitment of the inhibitory complex PP1c/GADD34 in polarizing neurons. Together, these results propose that SARA is a negative regulator of the TGFβ pathway, being critical for a proper orchestration for neuronal development.
Fil: Rozés Salvador, María Victoria. Universidad Nacional de Villa María. Instituto Académico Pedagógico de Ciencias Básicas y Aplicadas; Argentina. 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: Wilson Rodriguez, Carlos. 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. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina
Fil: Olmos, Cristina. Universidad de Chile; Chile
Fil: Gonzalez Billault, Christian. Universidad de Chile; Chile
Fil: Conde, Cecilia Beatriz. 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
description Neural development is a complex process that involves critical events, including cytoskeleton dynamics and selective trafficking of proteins to defined cellular destinations. In this regard, Smad Anchor for Receptor Activation (SARA) is an early endosome resident protein, where perform trafficking- associated functions. In addition, SARA is also involved in cell signaling, including the TGFβ-dependent pathway. Accordingly, SARA, and TGFβ signaling are required for proper axonal specification and migration of cortical neurons, unveiling a critical role for neuronal development. However, the cooperative action between the TGFβ pathway and SARA to this process has remained understudied. In this work, we show novel evidence suggesting a cross-talk between SARA and TGFβ pathway needed for proper polarization, axonal specification, growth and cortical migration of central neurons both in vitro and in vivo. Using microscopy tools and cultured hippocampal neurons, we show a local interaction between SARA and TβRI (TGFβ I receptor) at endosomes. In addition, SARA loss of function, induced by the expression of the dominant-negative SARA-F728A, over-activates the TGFβ pathway, most likely by preserving phosphorylated TβRI. Consequently, SARA-mediated activation of TGFβ pathway impacts on neuronal development, promoting axonal growth and cortical migration of neurons during brain development. Moreover, our data suggests that SARA basally prevents the activation of TβRI through the recruitment of the inhibitory complex PP1c/GADD34 in polarizing neurons. Together, these results propose that SARA is a negative regulator of the TGFβ pathway, being critical for a proper orchestration for neuronal development.
publishDate 2020
dc.date.none.fl_str_mv 2020-09
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/11336/140206
Rozés Salvador, María Victoria; Wilson Rodriguez, Carlos; Olmos, Cristina; Gonzalez Billault, Christian; Conde, Cecilia Beatriz; Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development; Frontiers Media S.A.; Frontiers in Cell and Developmental Biology; 8; 9-2020; 1-13
2296-634X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/140206
identifier_str_mv Rozés Salvador, María Victoria; Wilson Rodriguez, Carlos; Olmos, Cristina; Gonzalez Billault, Christian; Conde, Cecilia Beatriz; Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development; Frontiers Media S.A.; Frontiers in Cell and Developmental Biology; 8; 9-2020; 1-13
2296-634X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fcell.2020.550267
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 Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
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 13.22299

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