N-Cadherin Prodomain Processing Regulates Synaptogenesis

Autores
Reines, Analia Gabriela; Bernier, Louisn Philippe; McAdam, Robyn; Belkaid, Wiam; Shan, Weisong; Koch, Alexander W.; Séguéla, Philippe; Colman, David R.; Dhaunchak, Ajit S.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Classical cadherins, which are adhesion molecules functioning at the CNS synapse, are synthesized as adhesively inactive precursor proteins in the endoplasmic reticulum (ER). Signal sequence and prodomain cleavage in the ER and Golgi apparatus, respectively, activates their adhesive properties. Here, we provide the first evidence for sorting of nonadhesive precursor N-cadherin (ProN) to the neuronal surface, where it coexists with adhesively competent mature N-cadherin (N-cad), generating a spectrum of adhesive strengths. In cultured hippocampal neurons, a high ProN/N-cad ratio downregulates synapse formation. Neurons expressing genetically engineered uncleavable ProN make markedly fewer synapses. The synapse number can be rescued to normality by depleting surface ProN levels through prodomain cleavage by an exogenous protease. Finally, prodomain processing is developmentally regulated in the rat hippocampus. We conclude that it is the ProN/N-cad ratio and not mature N-cad alone that is critical for regulation of adhesion during synaptogenesis.
Fil: Reines, Analia Gabriela. McGill University; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Bernier, Louisn Philippe. McGill University; Canadá
Fil: McAdam, Robyn. McGill University; Canadá
Fil: Belkaid, Wiam. McGill University; Canadá
Fil: Shan, Weisong. McGill University; Canadá
Fil: Koch, Alexander W.. McGill University; Canadá
Fil: Séguéla, Philippe. McGill University; Canadá
Fil: Colman, David R.. McGill University; Canadá
Fil: Dhaunchak, Ajit S.. McGill University; Canadá
Materia
SYNAPTOGENESIS
N-CADHERIN
UNCLEAVED N-CADHERIN
DEVELOPMENT
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:11336/269475
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling N-Cadherin Prodomain Processing Regulates SynaptogenesisReines, Analia GabrielaBernier, Louisn PhilippeMcAdam, RobynBelkaid, WiamShan, WeisongKoch, Alexander W.Séguéla, PhilippeColman, David R.Dhaunchak, Ajit S.SYNAPTOGENESISN-CADHERINUNCLEAVED N-CADHERINDEVELOPMENThttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Classical cadherins, which are adhesion molecules functioning at the CNS synapse, are synthesized as adhesively inactive precursor proteins in the endoplasmic reticulum (ER). Signal sequence and prodomain cleavage in the ER and Golgi apparatus, respectively, activates their adhesive properties. Here, we provide the first evidence for sorting of nonadhesive precursor N-cadherin (ProN) to the neuronal surface, where it coexists with adhesively competent mature N-cadherin (N-cad), generating a spectrum of adhesive strengths. In cultured hippocampal neurons, a high ProN/N-cad ratio downregulates synapse formation. Neurons expressing genetically engineered uncleavable ProN make markedly fewer synapses. The synapse number can be rescued to normality by depleting surface ProN levels through prodomain cleavage by an exogenous protease. Finally, prodomain processing is developmentally regulated in the rat hippocampus. We conclude that it is the ProN/N-cad ratio and not mature N-cad alone that is critical for regulation of adhesion during synaptogenesis.Fil: Reines, Analia Gabriela. McGill University; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Bernier, Louisn Philippe. McGill University; CanadáFil: McAdam, Robyn. McGill University; CanadáFil: Belkaid, Wiam. McGill University; CanadáFil: Shan, Weisong. McGill University; CanadáFil: Koch, Alexander W.. McGill University; CanadáFil: Séguéla, Philippe. McGill University; CanadáFil: Colman, David R.. McGill University; CanadáFil: Dhaunchak, Ajit S.. McGill University; CanadáSociety for Neuroscience2012-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/269475Reines, Analia Gabriela; Bernier, Louisn Philippe; McAdam, Robyn; Belkaid, Wiam; Shan, Weisong; et al.; N-Cadherin Prodomain Processing Regulates Synaptogenesis; Society for Neuroscience; Journal of Neuroscience; 32; 18; 3-2012; 6323-63340270-6474CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.0916-12.2012info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/32/18/6323info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:01Zoai:ri.conicet.gov.ar:11336/269475instacron: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 09:55:01.545CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv N-Cadherin Prodomain Processing Regulates Synaptogenesis
title N-Cadherin Prodomain Processing Regulates Synaptogenesis
spellingShingle N-Cadherin Prodomain Processing Regulates Synaptogenesis
Reines, Analia Gabriela
SYNAPTOGENESIS
N-CADHERIN
UNCLEAVED N-CADHERIN
DEVELOPMENT
title_short N-Cadherin Prodomain Processing Regulates Synaptogenesis
title_full N-Cadherin Prodomain Processing Regulates Synaptogenesis
title_fullStr N-Cadherin Prodomain Processing Regulates Synaptogenesis
title_full_unstemmed N-Cadherin Prodomain Processing Regulates Synaptogenesis
title_sort N-Cadherin Prodomain Processing Regulates Synaptogenesis
dc.creator.none.fl_str_mv Reines, Analia Gabriela
Bernier, Louisn Philippe
McAdam, Robyn
Belkaid, Wiam
Shan, Weisong
Koch, Alexander W.
Séguéla, Philippe
Colman, David R.
Dhaunchak, Ajit S.
author Reines, Analia Gabriela
author_facet Reines, Analia Gabriela
Bernier, Louisn Philippe
McAdam, Robyn
Belkaid, Wiam
Shan, Weisong
Koch, Alexander W.
Séguéla, Philippe
Colman, David R.
Dhaunchak, Ajit S.
author_role author
author2 Bernier, Louisn Philippe
McAdam, Robyn
Belkaid, Wiam
Shan, Weisong
Koch, Alexander W.
Séguéla, Philippe
Colman, David R.
Dhaunchak, Ajit S.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv SYNAPTOGENESIS
N-CADHERIN
UNCLEAVED N-CADHERIN
DEVELOPMENT
topic SYNAPTOGENESIS
N-CADHERIN
UNCLEAVED N-CADHERIN
DEVELOPMENT
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Classical cadherins, which are adhesion molecules functioning at the CNS synapse, are synthesized as adhesively inactive precursor proteins in the endoplasmic reticulum (ER). Signal sequence and prodomain cleavage in the ER and Golgi apparatus, respectively, activates their adhesive properties. Here, we provide the first evidence for sorting of nonadhesive precursor N-cadherin (ProN) to the neuronal surface, where it coexists with adhesively competent mature N-cadherin (N-cad), generating a spectrum of adhesive strengths. In cultured hippocampal neurons, a high ProN/N-cad ratio downregulates synapse formation. Neurons expressing genetically engineered uncleavable ProN make markedly fewer synapses. The synapse number can be rescued to normality by depleting surface ProN levels through prodomain cleavage by an exogenous protease. Finally, prodomain processing is developmentally regulated in the rat hippocampus. We conclude that it is the ProN/N-cad ratio and not mature N-cad alone that is critical for regulation of adhesion during synaptogenesis.
Fil: Reines, Analia Gabriela. McGill University; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
Fil: Bernier, Louisn Philippe. McGill University; Canadá
Fil: McAdam, Robyn. McGill University; Canadá
Fil: Belkaid, Wiam. McGill University; Canadá
Fil: Shan, Weisong. McGill University; Canadá
Fil: Koch, Alexander W.. McGill University; Canadá
Fil: Séguéla, Philippe. McGill University; Canadá
Fil: Colman, David R.. McGill University; Canadá
Fil: Dhaunchak, Ajit S.. McGill University; Canadá
description Classical cadherins, which are adhesion molecules functioning at the CNS synapse, are synthesized as adhesively inactive precursor proteins in the endoplasmic reticulum (ER). Signal sequence and prodomain cleavage in the ER and Golgi apparatus, respectively, activates their adhesive properties. Here, we provide the first evidence for sorting of nonadhesive precursor N-cadherin (ProN) to the neuronal surface, where it coexists with adhesively competent mature N-cadherin (N-cad), generating a spectrum of adhesive strengths. In cultured hippocampal neurons, a high ProN/N-cad ratio downregulates synapse formation. Neurons expressing genetically engineered uncleavable ProN make markedly fewer synapses. The synapse number can be rescued to normality by depleting surface ProN levels through prodomain cleavage by an exogenous protease. Finally, prodomain processing is developmentally regulated in the rat hippocampus. We conclude that it is the ProN/N-cad ratio and not mature N-cad alone that is critical for regulation of adhesion during synaptogenesis.
publishDate 2012
dc.date.none.fl_str_mv 2012-03
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/11336/269475
Reines, Analia Gabriela; Bernier, Louisn Philippe; McAdam, Robyn; Belkaid, Wiam; Shan, Weisong; et al.; N-Cadherin Prodomain Processing Regulates Synaptogenesis; Society for Neuroscience; Journal of Neuroscience; 32; 18; 3-2012; 6323-6334
0270-6474
CONICET Digital
CONICET
url http://hdl.handle.net/11336/269475
identifier_str_mv Reines, Analia Gabriela; Bernier, Louisn Philippe; McAdam, Robyn; Belkaid, Wiam; Shan, Weisong; et al.; N-Cadherin Prodomain Processing Regulates Synaptogenesis; Society for Neuroscience; Journal of Neuroscience; 32; 18; 3-2012; 6323-6334
0270-6474
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.0916-12.2012
info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/32/18/6323
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
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_ 1842269319317159936
score 13.13397

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