Growth Cone Tctp Is Dynamically Regulated by Guidance Cues
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/107620 https://doi.org/10.3389/fnmol.2018.00399 |
Resumo: | Translationally controlled tumor protein (Tctp) contributes to retinal circuitry formation by promoting axon growth and guidance, but it remains unknown to what extent axonal Tctp specifically influences axon development programs. Various genome-wide profiling studies have ranked tctp transcripts among the most enriched in the axonal compartment of distinct neuronal populations, including embryonic retinal ganglion cells (RGCs), suggesting its expression can be regulated locally and that this may be important during development. Here, we report that growth cone Tctp levels change rapidly in response to Netrin-1 and Ephrin-A1, two guidance cues encountered by navigating RGC growth cones. This regulation is opposite in effect, as we observed protein synthesis- and mTORC1-dependent increases in growth cone Tctp levels after acute treatment with Netrin-1, but a decline upon exposure to Ephrin-A1, an inhibitor of mTORC1. Live imaging with translation reporters further showed that Netrin-1-induced synthesis of Tctp in growth cones is driven by a short 3'untranslated region (3'UTR) tctp mRNA isoform. However, acute inhibition of de novo Tctp synthesis in axons did not perturb the advance of retinal projections through the optic tract in vivo, indicating that locally produced Tctp is not necessary for normal axon growth and guidance. |
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Growth Cone Tctp Is Dynamically Regulated by Guidance CuesTctpmTORCNetrin-1Ephrin-A1axon guidanceretinal ganglion cellgrowth coneprotein translationTranslationally controlled tumor protein (Tctp) contributes to retinal circuitry formation by promoting axon growth and guidance, but it remains unknown to what extent axonal Tctp specifically influences axon development programs. Various genome-wide profiling studies have ranked tctp transcripts among the most enriched in the axonal compartment of distinct neuronal populations, including embryonic retinal ganglion cells (RGCs), suggesting its expression can be regulated locally and that this may be important during development. Here, we report that growth cone Tctp levels change rapidly in response to Netrin-1 and Ephrin-A1, two guidance cues encountered by navigating RGC growth cones. This regulation is opposite in effect, as we observed protein synthesis- and mTORC1-dependent increases in growth cone Tctp levels after acute treatment with Netrin-1, but a decline upon exposure to Ephrin-A1, an inhibitor of mTORC1. Live imaging with translation reporters further showed that Netrin-1-induced synthesis of Tctp in growth cones is driven by a short 3'untranslated region (3'UTR) tctp mRNA isoform. However, acute inhibition of de novo Tctp synthesis in axons did not perturb the advance of retinal projections through the optic tract in vivo, indicating that locally produced Tctp is not necessary for normal axon growth and guidance.Frontiers Media S.A.2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107620http://hdl.handle.net/10316/107620https://doi.org/10.3389/fnmol.2018.00399eng1662-5099Roque, Cláudio GouveiaHolt, Christine Einfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T11:44:45Zoai:estudogeral.uc.pt:10316/107620Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:57.206081Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Growth Cone Tctp Is Dynamically Regulated by Guidance Cues |
title |
Growth Cone Tctp Is Dynamically Regulated by Guidance Cues |
spellingShingle |
Growth Cone Tctp Is Dynamically Regulated by Guidance Cues Roque, Cláudio Gouveia Tctp mTORC Netrin-1 Ephrin-A1 axon guidance retinal ganglion cell growth cone protein translation |
title_short |
Growth Cone Tctp Is Dynamically Regulated by Guidance Cues |
title_full |
Growth Cone Tctp Is Dynamically Regulated by Guidance Cues |
title_fullStr |
Growth Cone Tctp Is Dynamically Regulated by Guidance Cues |
title_full_unstemmed |
Growth Cone Tctp Is Dynamically Regulated by Guidance Cues |
title_sort |
Growth Cone Tctp Is Dynamically Regulated by Guidance Cues |
author |
Roque, Cláudio Gouveia |
author_facet |
Roque, Cláudio Gouveia Holt, Christine E |
author_role |
author |
author2 |
Holt, Christine E |
author2_role |
author |
dc.contributor.author.fl_str_mv |
Roque, Cláudio Gouveia Holt, Christine E |
dc.subject.por.fl_str_mv |
Tctp mTORC Netrin-1 Ephrin-A1 axon guidance retinal ganglion cell growth cone protein translation |
topic |
Tctp mTORC Netrin-1 Ephrin-A1 axon guidance retinal ganglion cell growth cone protein translation |
description |
Translationally controlled tumor protein (Tctp) contributes to retinal circuitry formation by promoting axon growth and guidance, but it remains unknown to what extent axonal Tctp specifically influences axon development programs. Various genome-wide profiling studies have ranked tctp transcripts among the most enriched in the axonal compartment of distinct neuronal populations, including embryonic retinal ganglion cells (RGCs), suggesting its expression can be regulated locally and that this may be important during development. Here, we report that growth cone Tctp levels change rapidly in response to Netrin-1 and Ephrin-A1, two guidance cues encountered by navigating RGC growth cones. This regulation is opposite in effect, as we observed protein synthesis- and mTORC1-dependent increases in growth cone Tctp levels after acute treatment with Netrin-1, but a decline upon exposure to Ephrin-A1, an inhibitor of mTORC1. Live imaging with translation reporters further showed that Netrin-1-induced synthesis of Tctp in growth cones is driven by a short 3'untranslated region (3'UTR) tctp mRNA isoform. However, acute inhibition of de novo Tctp synthesis in axons did not perturb the advance of retinal projections through the optic tract in vivo, indicating that locally produced Tctp is not necessary for normal axon growth and guidance. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/107620 http://hdl.handle.net/10316/107620 https://doi.org/10.3389/fnmol.2018.00399 |
url |
http://hdl.handle.net/10316/107620 https://doi.org/10.3389/fnmol.2018.00399 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1662-5099 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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_version_ |
1799134125253197824 |