Dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) co-expression alters Ca V 2.2 modulation by G protein signaling cascades

Autores
Cordisco Gonzalez, Santiago; Mustafá, Emilio Román; Rodríguez, Silvia Susana; Perello, Mario; Raingo, Jesica
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Voltage-gated calcium channels type 2.2 (CaV2.2) are activated by action potentials at presynaptic terminals, and their calcium current induces neurotransmitter release. In this context, regulating CaV2.2 is critical, and one of the most important mechanisms for doing so is through is G protein-coupled receptor (GPCR) activity. Two such GPCRs are the ghrelin (GHSR) and the dopamine type 2 (D2R) receptors. We previously demonstrated that constitutive GHSR activity reduces CaV2.2 forward trafficking and that ghrelin-induced GHSR activity inhibits CaV2.2 currents. On the other hand, dopamine-induced D2R activity also inhibits CaV2.2 currents. It has been recently shown that D2R and GHSR form heteromers in hypothalamic neurons. This interaction profoundly changes the signaling cascades activated by dopamine and is necessary for dopamine-dependent anorexia. Here we explored how D2R-GHSR co-expression in HEK293T cells modulates the effect that each GPCR has on CaV2.2. We found that D2R-GHSR co-expression reduces the inhibition of CaV2.2 currents by agonist-induced D2R activation and added a new source of basal CaV2.2 current inhibition to the one produced by GHSR solely expression. We investigated the signaling cascades implicated and found that constitutive GHSR activity, Gq protein and Gβγ subunit play a critical role in these altered effects. Moreover, we found that the effect of D2R agonist on native calcium currents in hypothalamic neurons is reduced when both D2R and GHSR are over-expressed. In summary, our results allow us to propose a novel mechanism for controlling CaV2.2 currents involving the co-expression of two physiologically relevant GPCRs
Fil: Cordisco Gonzalez, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Mustafá, Emilio Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Rodríguez, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Perello, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Raingo, Jesica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Materia
CAV
DOPAMINA
D2R
GHSR
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:11336/127632
Acceder
id CONICETDig_8b2cceb852ea7b167f433cc5519cae2f
oai_identifier_str oai:ri.conicet.gov.ar:11336/127632
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) co-expression alters Ca V 2.2 modulation by G protein signaling cascadesCordisco Gonzalez, SantiagoMustafá, Emilio RománRodríguez, Silvia SusanaPerello, MarioRaingo, JesicaCAVDOPAMINAD2RGHSRhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Voltage-gated calcium channels type 2.2 (CaV2.2) are activated by action potentials at presynaptic terminals, and their calcium current induces neurotransmitter release. In this context, regulating CaV2.2 is critical, and one of the most important mechanisms for doing so is through is G protein-coupled receptor (GPCR) activity. Two such GPCRs are the ghrelin (GHSR) and the dopamine type 2 (D2R) receptors. We previously demonstrated that constitutive GHSR activity reduces CaV2.2 forward trafficking and that ghrelin-induced GHSR activity inhibits CaV2.2 currents. On the other hand, dopamine-induced D2R activity also inhibits CaV2.2 currents. It has been recently shown that D2R and GHSR form heteromers in hypothalamic neurons. This interaction profoundly changes the signaling cascades activated by dopamine and is necessary for dopamine-dependent anorexia. Here we explored how D2R-GHSR co-expression in HEK293T cells modulates the effect that each GPCR has on CaV2.2. We found that D2R-GHSR co-expression reduces the inhibition of CaV2.2 currents by agonist-induced D2R activation and added a new source of basal CaV2.2 current inhibition to the one produced by GHSR solely expression. We investigated the signaling cascades implicated and found that constitutive GHSR activity, Gq protein and Gβγ subunit play a critical role in these altered effects. Moreover, we found that the effect of D2R agonist on native calcium currents in hypothalamic neurons is reduced when both D2R and GHSR are over-expressed. In summary, our results allow us to propose a novel mechanism for controlling CaV2.2 currents involving the co-expression of two physiologically relevant GPCRsFil: Cordisco Gonzalez, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Mustafá, Emilio Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Rodríguez, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Perello, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Raingo, Jesica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaAmerican Chemical Society2019-12info: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/11336/127632Cordisco Gonzalez, Santiago; Mustafá, Emilio Román; Rodríguez, Silvia Susana; Perello, Mario; Raingo, Jesica; Dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) co-expression alters Ca V 2.2 modulation by G protein signaling cascades; American Chemical Society; ACS Chemical Neuroscience; 11; 1; 12-2019; 3-131948-7193CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acschemneuro.9b00426info:eu-repo/semantics/altIdentifier/doi/10.1021/acschemneuro.9b00426info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:52:11Zoai:ri.conicet.gov.ar:11336/127632instacron: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 09:52:12.244CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) co-expression alters Ca V 2.2 modulation by G protein signaling cascades
title Dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) co-expression alters Ca V 2.2 modulation by G protein signaling cascades
spellingShingle Dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) co-expression alters Ca V 2.2 modulation by G protein signaling cascades
Cordisco Gonzalez, Santiago
CAV
DOPAMINA
D2R
GHSR
title_short Dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) co-expression alters Ca V 2.2 modulation by G protein signaling cascades
title_full Dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) co-expression alters Ca V 2.2 modulation by G protein signaling cascades
title_fullStr Dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) co-expression alters Ca V 2.2 modulation by G protein signaling cascades
title_full_unstemmed Dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) co-expression alters Ca V 2.2 modulation by G protein signaling cascades
title_sort Dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) co-expression alters Ca V 2.2 modulation by G protein signaling cascades
dc.creator.none.fl_str_mv Cordisco Gonzalez, Santiago
Mustafá, Emilio Román
Rodríguez, Silvia Susana
Perello, Mario
Raingo, Jesica
author Cordisco Gonzalez, Santiago
author_facet Cordisco Gonzalez, Santiago
Mustafá, Emilio Román
Rodríguez, Silvia Susana
Perello, Mario
Raingo, Jesica
author_role author
author2 Mustafá, Emilio Román
Rodríguez, Silvia Susana
Perello, Mario
Raingo, Jesica
author2_role author
author
author
author
dc.subject.none.fl_str_mv CAV
DOPAMINA
D2R
GHSR
topic CAV
DOPAMINA
D2R
GHSR
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Voltage-gated calcium channels type 2.2 (CaV2.2) are activated by action potentials at presynaptic terminals, and their calcium current induces neurotransmitter release. In this context, regulating CaV2.2 is critical, and one of the most important mechanisms for doing so is through is G protein-coupled receptor (GPCR) activity. Two such GPCRs are the ghrelin (GHSR) and the dopamine type 2 (D2R) receptors. We previously demonstrated that constitutive GHSR activity reduces CaV2.2 forward trafficking and that ghrelin-induced GHSR activity inhibits CaV2.2 currents. On the other hand, dopamine-induced D2R activity also inhibits CaV2.2 currents. It has been recently shown that D2R and GHSR form heteromers in hypothalamic neurons. This interaction profoundly changes the signaling cascades activated by dopamine and is necessary for dopamine-dependent anorexia. Here we explored how D2R-GHSR co-expression in HEK293T cells modulates the effect that each GPCR has on CaV2.2. We found that D2R-GHSR co-expression reduces the inhibition of CaV2.2 currents by agonist-induced D2R activation and added a new source of basal CaV2.2 current inhibition to the one produced by GHSR solely expression. We investigated the signaling cascades implicated and found that constitutive GHSR activity, Gq protein and Gβγ subunit play a critical role in these altered effects. Moreover, we found that the effect of D2R agonist on native calcium currents in hypothalamic neurons is reduced when both D2R and GHSR are over-expressed. In summary, our results allow us to propose a novel mechanism for controlling CaV2.2 currents involving the co-expression of two physiologically relevant GPCRs
Fil: Cordisco Gonzalez, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Mustafá, Emilio Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Rodríguez, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Perello, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
Fil: Raingo, Jesica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina
description Voltage-gated calcium channels type 2.2 (CaV2.2) are activated by action potentials at presynaptic terminals, and their calcium current induces neurotransmitter release. In this context, regulating CaV2.2 is critical, and one of the most important mechanisms for doing so is through is G protein-coupled receptor (GPCR) activity. Two such GPCRs are the ghrelin (GHSR) and the dopamine type 2 (D2R) receptors. We previously demonstrated that constitutive GHSR activity reduces CaV2.2 forward trafficking and that ghrelin-induced GHSR activity inhibits CaV2.2 currents. On the other hand, dopamine-induced D2R activity also inhibits CaV2.2 currents. It has been recently shown that D2R and GHSR form heteromers in hypothalamic neurons. This interaction profoundly changes the signaling cascades activated by dopamine and is necessary for dopamine-dependent anorexia. Here we explored how D2R-GHSR co-expression in HEK293T cells modulates the effect that each GPCR has on CaV2.2. We found that D2R-GHSR co-expression reduces the inhibition of CaV2.2 currents by agonist-induced D2R activation and added a new source of basal CaV2.2 current inhibition to the one produced by GHSR solely expression. We investigated the signaling cascades implicated and found that constitutive GHSR activity, Gq protein and Gβγ subunit play a critical role in these altered effects. Moreover, we found that the effect of D2R agonist on native calcium currents in hypothalamic neurons is reduced when both D2R and GHSR are over-expressed. In summary, our results allow us to propose a novel mechanism for controlling CaV2.2 currents involving the co-expression of two physiologically relevant GPCRs
publishDate 2019
dc.date.none.fl_str_mv 2019-12
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/11336/127632
Cordisco Gonzalez, Santiago; Mustafá, Emilio Román; Rodríguez, Silvia Susana; Perello, Mario; Raingo, Jesica; Dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) co-expression alters Ca V 2.2 modulation by G protein signaling cascades; American Chemical Society; ACS Chemical Neuroscience; 11; 1; 12-2019; 3-13
1948-7193
CONICET Digital
CONICET
url http://hdl.handle.net/11336/127632
identifier_str_mv Cordisco Gonzalez, Santiago; Mustafá, Emilio Román; Rodríguez, Silvia Susana; Perello, Mario; Raingo, Jesica; Dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) co-expression alters Ca V 2.2 modulation by G protein signaling cascades; American Chemical Society; ACS Chemical Neuroscience; 11; 1; 12-2019; 3-13
1948-7193
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acschemneuro.9b00426
info:eu-repo/semantics/altIdentifier/doi/10.1021/acschemneuro.9b00426
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 American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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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