Role of the Wnt receptor Frizzled-1 presynaptic differentiation and function

BACKGROUND: The Wnt signaling pathway regulates several fundamental developmental processes and recently has been shown to be involved in different aspects of synaptic differentiation and plasticity. Some Wnt signaling components are localized at central synapses, and it is thus possible that this p...

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Autores: Varela-Nallar L., Grabowski C., Alfaro I., Alvarez A.,Inestrosa NC
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2009
País:Chile
Idioma:inglés
OAI Identifier:oai:repositorio.anid.cl:10533/237159
Acceso en línea:https://hdl.handle.net/10533/237159
Access Level:acceso abierto
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spelling Grabowski C., Alfaro I., Alvarez A.,Inestrosa NCVarela-Nallar L.200910.1186/1749-8104-4-41https://hdl.handle.net/10533/237159http://purl.org/coar/access_right/c_abf2Role of the Wnt receptor Frizzled-1 presynaptic differentiation and functionVarela-Nallar L.Grabowski C., Alfaro I., Alvarez A.,Inestrosa NC2019-12-18T18:14:53Z2022-07-07T22:05:30Z2019-12-18T18:14:53Z2022-07-07T22:05:30Z2009BACKGROUND: The Wnt signaling pathway regulates several fundamental developmental processes and recently has been shown to be involved in different aspects of synaptic differentiation and plasticity. Some Wnt signaling components are localized at central synapses, and it is thus possible that this pathway could be activated at the synapse. RESULTS: We examined the distribution of the Wnt receptor Frizzled-1 in cultured hippocampal neurons and determined that this receptor is located at synaptic contacts co-localizing with presynaptic proteins. Frizzled-1 was found in functional synapses detected with FM1-43 staining and in synaptic terminals from adult rat brain. Interestingly, overexpression of Frizzled-1 increased the number of clusters of Bassoon, a component of the active zone, while treatment with the extracellular cysteine-rich domain (CRD) of Frizzled-1 decreased Bassoon clustering, suggesting a role for this receptor in presynaptic differentiation. Consistent with this, treatment with the Frizzled-1 ligand Wnt-3a induced presynaptic protein clustering and increased functional presynaptic recycling sites, and these effects were prevented by co-treatment with the CRD of Frizzled-1. Moreover, in synaptically mature neurons Wnt-3a was able to modulate the kinetics of neurotransmitter release. CONCLUSION: Our results indicate that the activation of the Wnt pathway through Frizzled-1 occurs at the presynaptic level, and suggest that the synaptic effects of the Wnt signaling pathway could be modulated by local activation through synaptic Frizzled receptors.FONDAPFONDAP1398000113980001virtual::23648-1WOS:000272285700003https://hdl.handle.net/10533/237159enginstname: Conicytreponame: Repositorio Digital RI2.010.1186/1749-8104-4-41info:eu-repo/grantAgreement/Fondap/13980001https://www.ncbi.nlm.nih.gov/pubmed/19883499Atribución-NoComercial-SinDerivadas 3.0 Chilehttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/info:eu-repo/semantics/openAccessRole of the Wnt receptor Frizzled-1 presynaptic differentiation and functionNeural Dev.Articuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttps://hdl.handle.net/10533/237159http://purl.org/coar/resource_type/c_2df8fbb14c0c28ba-308a-47c1-afb7-2607f38e4c08virtual::23648-14c0c28ba-308a-47c1-afb7-2607f38e4c08virtual::23648-110533/237159oai:repositorio.anid.cl:10533/2371592023-07-24 18:54:16.286https://repositorio.anid.clRepositorio ANIDaletelier@anid.cl
dc.title.none.fl_str_mv Role of the Wnt receptor Frizzled-1 presynaptic differentiation and function
dc.title.journal.none.fl_str_mv Neural Dev.
title Role of the Wnt receptor Frizzled-1 presynaptic differentiation and function
spellingShingle Role of the Wnt receptor Frizzled-1 presynaptic differentiation and function
Varela-Nallar L.
title_short Role of the Wnt receptor Frizzled-1 presynaptic differentiation and function
title_full Role of the Wnt receptor Frizzled-1 presynaptic differentiation and function
title_fullStr Role of the Wnt receptor Frizzled-1 presynaptic differentiation and function
title_full_unstemmed Role of the Wnt receptor Frizzled-1 presynaptic differentiation and function
title_sort Role of the Wnt receptor Frizzled-1 presynaptic differentiation and function
dc.creator.none.fl_str_mv Varela-Nallar L.
Grabowski C., Alfaro I., Alvarez A.,Inestrosa NC
author Varela-Nallar L.
author_facet Varela-Nallar L.
Grabowski C., Alfaro I., Alvarez A.,Inestrosa NC
author_role author
author2 Grabowski C., Alfaro I., Alvarez A.,Inestrosa NC
author2_role author
description BACKGROUND: The Wnt signaling pathway regulates several fundamental developmental processes and recently has been shown to be involved in different aspects of synaptic differentiation and plasticity. Some Wnt signaling components are localized at central synapses, and it is thus possible that this pathway could be activated at the synapse. RESULTS: We examined the distribution of the Wnt receptor Frizzled-1 in cultured hippocampal neurons and determined that this receptor is located at synaptic contacts co-localizing with presynaptic proteins. Frizzled-1 was found in functional synapses detected with FM1-43 staining and in synaptic terminals from adult rat brain. Interestingly, overexpression of Frizzled-1 increased the number of clusters of Bassoon, a component of the active zone, while treatment with the extracellular cysteine-rich domain (CRD) of Frizzled-1 decreased Bassoon clustering, suggesting a role for this receptor in presynaptic differentiation. Consistent with this, treatment with the Frizzled-1 ligand Wnt-3a induced presynaptic protein clustering and increased functional presynaptic recycling sites, and these effects were prevented by co-treatment with the CRD of Frizzled-1. Moreover, in synaptically mature neurons Wnt-3a was able to modulate the kinetics of neurotransmitter release. CONCLUSION: Our results indicate that the activation of the Wnt pathway through Frizzled-1 occurs at the presynaptic level, and suggest that the synaptic effects of the Wnt signaling pathway could be modulated by local activation through synaptic Frizzled receptors.
publishDate 2009
dc.date.issued.none.fl_str_mv 2009
dc.date.accessioned.none.fl_str_mv 2019-12-18T18:14:53Z
2022-07-07T22:05:30Z
dc.date.available.none.fl_str_mv 2019-12-18T18:14:53Z
2022-07-07T22:05:30Z
dc.type.none.fl_str_mv Articulo
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.openaire.none.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.folio.none.fl_str_mv 13980001
13980001
dc.identifier.idwos.none.fl_str_mv WOS:000272285700003
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10533/237159
identifier_str_mv 13980001
WOS:000272285700003
url https://hdl.handle.net/10533/237159
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv instname: Conicyt
reponame: Repositorio Digital RI2.0
dc.relation.doi.none.fl_str_mv 10.1186/1749-8104-4-41
dc.relation.projectid.none.fl_str_mv info:eu-repo/grantAgreement/Fondap/13980001
dc.relation.uri.none.fl_str_mv https://www.ncbi.nlm.nih.gov/pubmed/19883499
dc.rights.none.fl_str_mv Atribución-NoComercial-SinDerivadas 3.0 Chile
http://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rights.driver.none.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv Atribución-NoComercial-SinDerivadas 3.0 Chile
http://creativecommons.org/licenses/by-nc-nd/3.0/cl/
eu_rights_str_mv openAccess
repository.name.fl_str_mv Repositorio ANID
repository.mail.fl_str_mv aletelier@anid.cl
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