TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo

Autores
Belkacemi, Thabet; Niermann, Alexander; Hofmann, Laura; Wissenbach, Ulrich; Birnbaumer, Lutz; Leidinger, Petra; Backes, Christina; Meese, Eckart; Keller, Andreas; Bai, Xianshu; Scheller, Anja; Kirchhoff, Frank; Philipp, Stephan E.; Weissgerber, Petra; Flockerzi, Veit; Beck, Andreas
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca2+. Transient receptor potential canonical (TRPC) channels may contribute to Ca2+ influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells. Ca2+ entry in cortical astrocytes depended on TRPC3 and was increased in the absence of Trpc1. After co-expression of Trpc1 and Trpc3 in HEK-293 cells both proteins co-immunoprecipitate and form functional heteromeric channels, with TRPC1 reducing TRPC3 activity. In vitro, lack of Trpc3 reduced astrocyte proliferation and migration whereas the TRPC3 gain-of-function moonwalker mutation and Trpc1 deficiency increased astrocyte migration. In vivo, astrogliosis and cortex edema following stab wound injury were reduced in Trpc3-/- but increased in Trpc1-/- mice. In summary, our results show a decisive contribution of TRPC3 to astrocyte Ca2+ signaling, which is even augmented in the absence of Trpc1, in particular following brain injury. Targeted therapies to reduce TRPC3 channel activity in astrocytes might therefore be beneficial in traumatic brain injury.
Fil: Belkacemi, Thabet. Universitat Saarland; Alemania
Fil: Niermann, Alexander. Universitat Saarland; Alemania
Fil: Hofmann, Laura. Universitat Saarland; Alemania
Fil: Wissenbach, Ulrich. Universitat Saarland; Alemania
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina ; Argentina. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Leidinger, Petra. Universitat Saarland; Alemania
Fil: Backes, Christina. Universitat Saarland; Alemania
Fil: Meese, Eckart. Universitat Saarland; Alemania
Fil: Keller, Andreas. Universitat Saarland; Alemania
Fil: Bai, Xianshu. Universitat Saarland; Alemania
Fil: Scheller, Anja. Universitat Saarland; Alemania
Fil: Kirchhoff, Frank. Universitat Saarland; Alemania
Fil: Philipp, Stephan E.. Universitat Saarland; Alemania
Fil: Weissgerber, Petra. Universitat Saarland; Alemania
Fil: Flockerzi, Veit. Universitat Saarland; Alemania
Fil: Beck, Andreas. Universitat Saarland; Alemania
Materia
Glia
Ion Channels
Membrane Currents
Migration
Proliferation
Stab Wound Injury
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:11336/49949
Acceder
id CONICETDig_a75a4439b99d63b6aab47e0dc2f44b58
oai_identifier_str oai:ri.conicet.gov.ar:11336/49949
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivoBelkacemi, ThabetNiermann, AlexanderHofmann, LauraWissenbach, UlrichBirnbaumer, LutzLeidinger, PetraBackes, ChristinaMeese, EckartKeller, AndreasBai, XianshuScheller, AnjaKirchhoff, FrankPhilipp, Stephan E.Weissgerber, PetraFlockerzi, VeitBeck, AndreasGliaIon ChannelsMembrane CurrentsMigrationProliferationStab Wound Injuryhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca2+. Transient receptor potential canonical (TRPC) channels may contribute to Ca2+ influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells. Ca2+ entry in cortical astrocytes depended on TRPC3 and was increased in the absence of Trpc1. After co-expression of Trpc1 and Trpc3 in HEK-293 cells both proteins co-immunoprecipitate and form functional heteromeric channels, with TRPC1 reducing TRPC3 activity. In vitro, lack of Trpc3 reduced astrocyte proliferation and migration whereas the TRPC3 gain-of-function moonwalker mutation and Trpc1 deficiency increased astrocyte migration. In vivo, astrogliosis and cortex edema following stab wound injury were reduced in Trpc3-/- but increased in Trpc1-/- mice. In summary, our results show a decisive contribution of TRPC3 to astrocyte Ca2+ signaling, which is even augmented in the absence of Trpc1, in particular following brain injury. Targeted therapies to reduce TRPC3 channel activity in astrocytes might therefore be beneficial in traumatic brain injury.Fil: Belkacemi, Thabet. Universitat Saarland; AlemaniaFil: Niermann, Alexander. Universitat Saarland; AlemaniaFil: Hofmann, Laura. Universitat Saarland; AlemaniaFil: Wissenbach, Ulrich. Universitat Saarland; AlemaniaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina ; Argentina. National Institute of Environmental Health Sciences; Estados UnidosFil: Leidinger, Petra. Universitat Saarland; AlemaniaFil: Backes, Christina. Universitat Saarland; AlemaniaFil: Meese, Eckart. Universitat Saarland; AlemaniaFil: Keller, Andreas. Universitat Saarland; AlemaniaFil: Bai, Xianshu. Universitat Saarland; AlemaniaFil: Scheller, Anja. Universitat Saarland; AlemaniaFil: Kirchhoff, Frank. Universitat Saarland; AlemaniaFil: Philipp, Stephan E.. Universitat Saarland; AlemaniaFil: Weissgerber, Petra. Universitat Saarland; AlemaniaFil: Flockerzi, Veit. Universitat Saarland; AlemaniaFil: Beck, Andreas. Universitat Saarland; AlemaniaWiley-liss, Div John Wiley & Sons Inc2017-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/49949Belkacemi, Thabet; Niermann, Alexander; Hofmann, Laura; Wissenbach, Ulrich; Birnbaumer, Lutz; et al.; TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo; Wiley-liss, Div John Wiley & Sons Inc; Glia; 65; 9; 6-2017; 1535-15490894-14911098-1136CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/glia.23180info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/glia.23180info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:05:26Zoai:ri.conicet.gov.ar:11336/49949instacron: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 10:05:26.911CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
spellingShingle TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
Belkacemi, Thabet
Glia
Ion Channels
Membrane Currents
Migration
Proliferation
Stab Wound Injury
title_short TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title_full TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title_fullStr TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title_full_unstemmed TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
title_sort TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo
dc.creator.none.fl_str_mv Belkacemi, Thabet
Niermann, Alexander
Hofmann, Laura
Wissenbach, Ulrich
Birnbaumer, Lutz
Leidinger, Petra
Backes, Christina
Meese, Eckart
Keller, Andreas
Bai, Xianshu
Scheller, Anja
Kirchhoff, Frank
Philipp, Stephan E.
Weissgerber, Petra
Flockerzi, Veit
Beck, Andreas
author Belkacemi, Thabet
author_facet Belkacemi, Thabet
Niermann, Alexander
Hofmann, Laura
Wissenbach, Ulrich
Birnbaumer, Lutz
Leidinger, Petra
Backes, Christina
Meese, Eckart
Keller, Andreas
Bai, Xianshu
Scheller, Anja
Kirchhoff, Frank
Philipp, Stephan E.
Weissgerber, Petra
Flockerzi, Veit
Beck, Andreas
author_role author
author2 Niermann, Alexander
Hofmann, Laura
Wissenbach, Ulrich
Birnbaumer, Lutz
Leidinger, Petra
Backes, Christina
Meese, Eckart
Keller, Andreas
Bai, Xianshu
Scheller, Anja
Kirchhoff, Frank
Philipp, Stephan E.
Weissgerber, Petra
Flockerzi, Veit
Beck, Andreas
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Glia
Ion Channels
Membrane Currents
Migration
Proliferation
Stab Wound Injury
topic Glia
Ion Channels
Membrane Currents
Migration
Proliferation
Stab Wound Injury
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca2+. Transient receptor potential canonical (TRPC) channels may contribute to Ca2+ influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells. Ca2+ entry in cortical astrocytes depended on TRPC3 and was increased in the absence of Trpc1. After co-expression of Trpc1 and Trpc3 in HEK-293 cells both proteins co-immunoprecipitate and form functional heteromeric channels, with TRPC1 reducing TRPC3 activity. In vitro, lack of Trpc3 reduced astrocyte proliferation and migration whereas the TRPC3 gain-of-function moonwalker mutation and Trpc1 deficiency increased astrocyte migration. In vivo, astrogliosis and cortex edema following stab wound injury were reduced in Trpc3-/- but increased in Trpc1-/- mice. In summary, our results show a decisive contribution of TRPC3 to astrocyte Ca2+ signaling, which is even augmented in the absence of Trpc1, in particular following brain injury. Targeted therapies to reduce TRPC3 channel activity in astrocytes might therefore be beneficial in traumatic brain injury.
Fil: Belkacemi, Thabet. Universitat Saarland; Alemania
Fil: Niermann, Alexander. Universitat Saarland; Alemania
Fil: Hofmann, Laura. Universitat Saarland; Alemania
Fil: Wissenbach, Ulrich. Universitat Saarland; Alemania
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina ; Argentina. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Leidinger, Petra. Universitat Saarland; Alemania
Fil: Backes, Christina. Universitat Saarland; Alemania
Fil: Meese, Eckart. Universitat Saarland; Alemania
Fil: Keller, Andreas. Universitat Saarland; Alemania
Fil: Bai, Xianshu. Universitat Saarland; Alemania
Fil: Scheller, Anja. Universitat Saarland; Alemania
Fil: Kirchhoff, Frank. Universitat Saarland; Alemania
Fil: Philipp, Stephan E.. Universitat Saarland; Alemania
Fil: Weissgerber, Petra. Universitat Saarland; Alemania
Fil: Flockerzi, Veit. Universitat Saarland; Alemania
Fil: Beck, Andreas. Universitat Saarland; Alemania
description Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca2+. Transient receptor potential canonical (TRPC) channels may contribute to Ca2+ influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells. Ca2+ entry in cortical astrocytes depended on TRPC3 and was increased in the absence of Trpc1. After co-expression of Trpc1 and Trpc3 in HEK-293 cells both proteins co-immunoprecipitate and form functional heteromeric channels, with TRPC1 reducing TRPC3 activity. In vitro, lack of Trpc3 reduced astrocyte proliferation and migration whereas the TRPC3 gain-of-function moonwalker mutation and Trpc1 deficiency increased astrocyte migration. In vivo, astrogliosis and cortex edema following stab wound injury were reduced in Trpc3-/- but increased in Trpc1-/- mice. In summary, our results show a decisive contribution of TRPC3 to astrocyte Ca2+ signaling, which is even augmented in the absence of Trpc1, in particular following brain injury. Targeted therapies to reduce TRPC3 channel activity in astrocytes might therefore be beneficial in traumatic brain injury.
publishDate 2017
dc.date.none.fl_str_mv 2017-06
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/11336/49949
Belkacemi, Thabet; Niermann, Alexander; Hofmann, Laura; Wissenbach, Ulrich; Birnbaumer, Lutz; et al.; TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo; Wiley-liss, Div John Wiley & Sons Inc; Glia; 65; 9; 6-2017; 1535-1549
0894-1491
1098-1136
CONICET Digital
CONICET
url http://hdl.handle.net/11336/49949
identifier_str_mv Belkacemi, Thabet; Niermann, Alexander; Hofmann, Laura; Wissenbach, Ulrich; Birnbaumer, Lutz; et al.; TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo; Wiley-liss, Div John Wiley & Sons Inc; Glia; 65; 9; 6-2017; 1535-1549
0894-1491
1098-1136
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/glia.23180
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/glia.23180
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 Wiley-liss, Div John Wiley & Sons Inc
publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
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 13.13397

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