Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons

Autores
Heinzt, Tristan; Heller, Janosh P.; Zhao, Rongrong; Caceres, Alfredo Oscar; Eva, RIchard; Fawcett, James E.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
CNS axons have poor regenerative ability compared to PNS axons, and mature axons regenerate less well than immature embryonic axons. The loss of regenerative ability with maturity is accompanied by the setting up of a selective transport filter in axons, restricting the types of molecule that are present. We confirm that integrins (represented by subunits β1 and α5) are present in early cortical axons in vitro but are excluded from mature axons. Ribosomal protein and L1 show selective axonal transport through association with kinesin kif4A; we have therefore examined the hypothesis that integrin transport might also be in association with kif4A. Kif4A is present in all processes of immature cortical neurons cultured at E18, then downregulated by 14 days in vitro, coinciding with the exclusion of integrin from axons. Kif4a co-localises with β1 integrin in vesicles in neurons and non-neuronal cells, and the two molecules co-immunoprecipitate. Knockdown of KIF4A expression with shRNA reduced the level of integrin β1 in axons of developing neurons and reduced neurite elongation on laminin, an integrin-dependent substrate. Overexpression of kif4A triggered apoptosis in neuronal and non-neuronal cells. In mature neurons expression of kif4A-GFP at a modest level did not kill the cells, and the kif4A was detectable in their axons. However this was not accompanied by an increase in integrin β1 axonal transport, suggesting that kif4A is not the only integrin transporter, and that integrin exclusion from axons is controlled by factors other than the kif4A level.
Fil: Heinzt, Tristan. University of Cambridge; Reino Unido
Fil: Heller, Janosh P.. University of Cambridge; Reino Unido
Fil: Zhao, Rongrong. University of Cambridge; Reino Unido
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: Eva, RIchard. University of Cambridge; Reino Unido
Fil: Fawcett, James E.. University of Cambridge; Reino Unido
Materia
Axon
Axon Transport
Axon Growth
Integrin
Trafficking
Kinesin
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:11336/31638

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network_name_str CONICET Digital (CONICET)
spelling Kinesin KIF4A transports integrin β1 in developing axons of cortical neuronsHeinzt, TristanHeller, Janosh P.Zhao, RongrongCaceres, Alfredo OscarEva, RIchardFawcett, James E.AxonAxon TransportAxon GrowthIntegrinTraffickingKinesinhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3CNS axons have poor regenerative ability compared to PNS axons, and mature axons regenerate less well than immature embryonic axons. The loss of regenerative ability with maturity is accompanied by the setting up of a selective transport filter in axons, restricting the types of molecule that are present. We confirm that integrins (represented by subunits β1 and α5) are present in early cortical axons in vitro but are excluded from mature axons. Ribosomal protein and L1 show selective axonal transport through association with kinesin kif4A; we have therefore examined the hypothesis that integrin transport might also be in association with kif4A. Kif4A is present in all processes of immature cortical neurons cultured at E18, then downregulated by 14 days in vitro, coinciding with the exclusion of integrin from axons. Kif4a co-localises with β1 integrin in vesicles in neurons and non-neuronal cells, and the two molecules co-immunoprecipitate. Knockdown of KIF4A expression with shRNA reduced the level of integrin β1 in axons of developing neurons and reduced neurite elongation on laminin, an integrin-dependent substrate. Overexpression of kif4A triggered apoptosis in neuronal and non-neuronal cells. In mature neurons expression of kif4A-GFP at a modest level did not kill the cells, and the kif4A was detectable in their axons. However this was not accompanied by an increase in integrin β1 axonal transport, suggesting that kif4A is not the only integrin transporter, and that integrin exclusion from axons is controlled by factors other than the kif4A level.Fil: Heinzt, Tristan. University of Cambridge; Reino UnidoFil: Heller, Janosh P.. University of Cambridge; Reino UnidoFil: Zhao, Rongrong. University of Cambridge; Reino UnidoFil: 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: Eva, RIchard. University of Cambridge; Reino UnidoFil: Fawcett, James E.. University of Cambridge; Reino UnidoAcademic Press Inc Elsevier Science2014-09info: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/11336/31638Fawcett, James E.; Caceres, Alfredo Oscar; Heinzt, Tristan; Zhao, Rongrong; Heller, Janosh P.; Eva, RIchard; et al.; Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons; Academic Press Inc Elsevier Science; Molecular and Cellular Neuroscience; 63; 9-2014; 60-711044-7431CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.mcn.2014.09.003info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1044743114001638info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:30:27Zoai:ri.conicet.gov.ar:11336/31638instacron: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 15:30:28.077CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons
title Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons
spellingShingle Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons
Heinzt, Tristan
Axon
Axon Transport
Axon Growth
Integrin
Trafficking
Kinesin
title_short Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons
title_full Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons
title_fullStr Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons
title_full_unstemmed Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons
title_sort Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons
dc.creator.none.fl_str_mv Heinzt, Tristan
Heller, Janosh P.
Zhao, Rongrong
Caceres, Alfredo Oscar
Eva, RIchard
Fawcett, James E.
author Heinzt, Tristan
author_facet Heinzt, Tristan
Heller, Janosh P.
Zhao, Rongrong
Caceres, Alfredo Oscar
Eva, RIchard
Fawcett, James E.
author_role author
author2 Heller, Janosh P.
Zhao, Rongrong
Caceres, Alfredo Oscar
Eva, RIchard
Fawcett, James E.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Axon
Axon Transport
Axon Growth
Integrin
Trafficking
Kinesin
topic Axon
Axon Transport
Axon Growth
Integrin
Trafficking
Kinesin
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv CNS axons have poor regenerative ability compared to PNS axons, and mature axons regenerate less well than immature embryonic axons. The loss of regenerative ability with maturity is accompanied by the setting up of a selective transport filter in axons, restricting the types of molecule that are present. We confirm that integrins (represented by subunits β1 and α5) are present in early cortical axons in vitro but are excluded from mature axons. Ribosomal protein and L1 show selective axonal transport through association with kinesin kif4A; we have therefore examined the hypothesis that integrin transport might also be in association with kif4A. Kif4A is present in all processes of immature cortical neurons cultured at E18, then downregulated by 14 days in vitro, coinciding with the exclusion of integrin from axons. Kif4a co-localises with β1 integrin in vesicles in neurons and non-neuronal cells, and the two molecules co-immunoprecipitate. Knockdown of KIF4A expression with shRNA reduced the level of integrin β1 in axons of developing neurons and reduced neurite elongation on laminin, an integrin-dependent substrate. Overexpression of kif4A triggered apoptosis in neuronal and non-neuronal cells. In mature neurons expression of kif4A-GFP at a modest level did not kill the cells, and the kif4A was detectable in their axons. However this was not accompanied by an increase in integrin β1 axonal transport, suggesting that kif4A is not the only integrin transporter, and that integrin exclusion from axons is controlled by factors other than the kif4A level.
Fil: Heinzt, Tristan. University of Cambridge; Reino Unido
Fil: Heller, Janosh P.. University of Cambridge; Reino Unido
Fil: Zhao, Rongrong. University of Cambridge; Reino Unido
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: Eva, RIchard. University of Cambridge; Reino Unido
Fil: Fawcett, James E.. University of Cambridge; Reino Unido
description CNS axons have poor regenerative ability compared to PNS axons, and mature axons regenerate less well than immature embryonic axons. The loss of regenerative ability with maturity is accompanied by the setting up of a selective transport filter in axons, restricting the types of molecule that are present. We confirm that integrins (represented by subunits β1 and α5) are present in early cortical axons in vitro but are excluded from mature axons. Ribosomal protein and L1 show selective axonal transport through association with kinesin kif4A; we have therefore examined the hypothesis that integrin transport might also be in association with kif4A. Kif4A is present in all processes of immature cortical neurons cultured at E18, then downregulated by 14 days in vitro, coinciding with the exclusion of integrin from axons. Kif4a co-localises with β1 integrin in vesicles in neurons and non-neuronal cells, and the two molecules co-immunoprecipitate. Knockdown of KIF4A expression with shRNA reduced the level of integrin β1 in axons of developing neurons and reduced neurite elongation on laminin, an integrin-dependent substrate. Overexpression of kif4A triggered apoptosis in neuronal and non-neuronal cells. In mature neurons expression of kif4A-GFP at a modest level did not kill the cells, and the kif4A was detectable in their axons. However this was not accompanied by an increase in integrin β1 axonal transport, suggesting that kif4A is not the only integrin transporter, and that integrin exclusion from axons is controlled by factors other than the kif4A level.
publishDate 2014
dc.date.none.fl_str_mv 2014-09
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/11336/31638
Fawcett, James E.; Caceres, Alfredo Oscar; Heinzt, Tristan; Zhao, Rongrong; Heller, Janosh P.; Eva, RIchard; et al.; Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons; Academic Press Inc Elsevier Science; Molecular and Cellular Neuroscience; 63; 9-2014; 60-71
1044-7431
CONICET Digital
CONICET
url http://hdl.handle.net/11336/31638
identifier_str_mv Fawcett, James E.; Caceres, Alfredo Oscar; Heinzt, Tristan; Zhao, Rongrong; Heller, Janosh P.; Eva, RIchard; et al.; Kinesin KIF4A transports integrin β1 in developing axons of cortical neurons; Academic Press Inc Elsevier Science; Molecular and Cellular Neuroscience; 63; 9-2014; 60-71
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.2014.09.003
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1044743114001638
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 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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