Gao is a major determinant of cAMP signaling in the pathophysiology of movement disorders

Autores
Muntean, Brian S.; Masuho, Ikuo; Dao, Maria; Blakely, Randy D.; Grill, Brock; Martemyanov, Kirill A.; Sutton, Laurie; Zucca, Stefano; Iwamoto, Hideki; Patil, Dipak N.; Wang, Dandan; Birnbaumer, Lutz
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fil: Muntean, Brian S. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Masuho, Ikuo. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Dao, Maria. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Sutton, Laurie. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Zucca, Stefano. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Iwamoto, Hideki. Universidad Atlántica de Florida. Facultad de Medicina. Departamento de Ciencias Biomédicas e Instituto del Cerebro; Estados Unidos
Fil: Patil, Dipak N. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Wang, Dandan. Instituto de Investigación Infantil de Seattle. Centro de Investigación Integrativa del Cerebro; Estados Unidos
Fil: Birnbaumer, Lutz. Instituto Nacional de Ciencias de la Salud Ambiental. Laboratorio de neurobiología; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Blakely, Randy D. Universidad Atlántica de Florida. Facultad de Medicina. Departamento de Ciencias Biomédicas e Instituto del Cerebro; Estados Unidos
Fil: Grill, Brock. Instituto de Investigación Infantil de Seattle. Centro de Investigación Integrativa del Cerebro; Estados Unidos
Fil: Grill, Brock. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Grill, Brock. Universidad de Washington; Estados Unidos
Fil: Martemyanov, Kirill A. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Abstract: The G protein alpha subunit o (Gao) is one of the most abundant proteins in the nervous system, and pathogenic mutations in its gene (GNAO1) cause movement disorder. However, the function of Gao is ill defined mechanistically. Here, we show that Gao dictates neuromodulatory responsiveness of striatal neurons and is required for movement control. Using in vivo optical sensors and enzymatic assays, we determine that Gao provides a separate transduction channel that modulates coupling of both inhibitory and stimulatory dopamine receptors to the cyclic AMP (cAMP)-generating enzyme adenylyl cyclase. Through a combination of cell-based assays and rodent models, we demonstrate that GNAO1-associated mutations alter Gao function in a neuron-type-specific fashion via a combination of a dominant-negative and loss-of-function mechanisms. Overall, our findings suggest thatGao and its pathological variants function in specific circuits to regulate neuromodulatory signals essential for executing motor programs.
Fuente
Cell Reports. 2021, 34
Materia
PROTEINAS
CELULAS
FISIOLOGIA
NEUROFISIOLOGIA
QUIMICA CELULAR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
Repositorio Institucional (UCA)
Institución
Pontificia Universidad Católica Argentina
OAI Identificador
oai:ucacris:123456789/11617
Acceder
id RIUCA_946eaa744a28aff9d85edaa6c2bbde1d
oai_identifier_str oai:ucacris:123456789/11617
network_acronym_str RIUCA
repository_id_str 2585
network_name_str Repositorio Institucional (UCA)
spelling Gao is a major determinant of cAMP signaling in the pathophysiology of movement disordersMuntean, Brian S.Masuho, IkuoDao, MariaBlakely, Randy D.Grill, BrockMartemyanov, Kirill A.Sutton, LaurieZucca, StefanoIwamoto, HidekiPatil, Dipak N.Wang, DandanBirnbaumer, LutzPROTEINASCELULASFISIOLOGIANEUROFISIOLOGIAQUIMICA CELULARFil: Muntean, Brian S. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados UnidosFil: Masuho, Ikuo. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados UnidosFil: Dao, Maria. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados UnidosFil: Sutton, Laurie. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados UnidosFil: Zucca, Stefano. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados UnidosFil: Iwamoto, Hideki. Universidad Atlántica de Florida. Facultad de Medicina. Departamento de Ciencias Biomédicas e Instituto del Cerebro; Estados UnidosFil: Patil, Dipak N. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados UnidosFil: Wang, Dandan. Instituto de Investigación Infantil de Seattle. Centro de Investigación Integrativa del Cerebro; Estados UnidosFil: Birnbaumer, Lutz. Instituto Nacional de Ciencias de la Salud Ambiental. Laboratorio de neurobiología; Estados UnidosFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Blakely, Randy D. Universidad Atlántica de Florida. Facultad de Medicina. Departamento de Ciencias Biomédicas e Instituto del Cerebro; Estados UnidosFil: Grill, Brock. Instituto de Investigación Infantil de Seattle. Centro de Investigación Integrativa del Cerebro; Estados UnidosFil: Grill, Brock. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados UnidosFil: Grill, Brock. Universidad de Washington; Estados UnidosFil: Martemyanov, Kirill A. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados UnidosAbstract: The G protein alpha subunit o (Gao) is one of the most abundant proteins in the nervous system, and pathogenic mutations in its gene (GNAO1) cause movement disorder. However, the function of Gao is ill defined mechanistically. Here, we show that Gao dictates neuromodulatory responsiveness of striatal neurons and is required for movement control. Using in vivo optical sensors and enzymatic assays, we determine that Gao provides a separate transduction channel that modulates coupling of both inhibitory and stimulatory dopamine receptors to the cyclic AMP (cAMP)-generating enzyme adenylyl cyclase. Through a combination of cell-based assays and rodent models, we demonstrate that GNAO1-associated mutations alter Gao function in a neuron-type-specific fashion via a combination of a dominant-negative and loss-of-function mechanisms. Overall, our findings suggest thatGao and its pathological variants function in specific circuits to regulate neuromodulatory signals essential for executing motor programs.Elsevier2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/116172211-1247 (on line)10.1016/j.celrep.2021.108718ll33535037Muntean, B., et al. Gao is a major determinant of cAMP signaling in the pathophysiology of movement disorders [en línea]. Cell Reports. 2021, 34. doi: 10.1016/j.celrep.2021.108718ll. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/11617Cell Reports. 2021, 34reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:57:51Zoai:ucacris:123456789/11617instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:57:51.655Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse
dc.title.none.fl_str_mv Gao is a major determinant of cAMP signaling in the pathophysiology of movement disorders
title Gao is a major determinant of cAMP signaling in the pathophysiology of movement disorders
spellingShingle Gao is a major determinant of cAMP signaling in the pathophysiology of movement disorders
Muntean, Brian S.
PROTEINAS
CELULAS
FISIOLOGIA
NEUROFISIOLOGIA
QUIMICA CELULAR
title_short Gao is a major determinant of cAMP signaling in the pathophysiology of movement disorders
title_full Gao is a major determinant of cAMP signaling in the pathophysiology of movement disorders
title_fullStr Gao is a major determinant of cAMP signaling in the pathophysiology of movement disorders
title_full_unstemmed Gao is a major determinant of cAMP signaling in the pathophysiology of movement disorders
title_sort Gao is a major determinant of cAMP signaling in the pathophysiology of movement disorders
dc.creator.none.fl_str_mv Muntean, Brian S.
Masuho, Ikuo
Dao, Maria
Blakely, Randy D.
Grill, Brock
Martemyanov, Kirill A.
Sutton, Laurie
Zucca, Stefano
Iwamoto, Hideki
Patil, Dipak N.
Wang, Dandan
Birnbaumer, Lutz
author Muntean, Brian S.
author_facet Muntean, Brian S.
Masuho, Ikuo
Dao, Maria
Blakely, Randy D.
Grill, Brock
Martemyanov, Kirill A.
Sutton, Laurie
Zucca, Stefano
Iwamoto, Hideki
Patil, Dipak N.
Wang, Dandan
Birnbaumer, Lutz
author_role author
author2 Masuho, Ikuo
Dao, Maria
Blakely, Randy D.
Grill, Brock
Martemyanov, Kirill A.
Sutton, Laurie
Zucca, Stefano
Iwamoto, Hideki
Patil, Dipak N.
Wang, Dandan
Birnbaumer, Lutz
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PROTEINAS
CELULAS
FISIOLOGIA
NEUROFISIOLOGIA
QUIMICA CELULAR
topic PROTEINAS
CELULAS
FISIOLOGIA
NEUROFISIOLOGIA
QUIMICA CELULAR
dc.description.none.fl_txt_mv Fil: Muntean, Brian S. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Masuho, Ikuo. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Dao, Maria. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Sutton, Laurie. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Zucca, Stefano. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Iwamoto, Hideki. Universidad Atlántica de Florida. Facultad de Medicina. Departamento de Ciencias Biomédicas e Instituto del Cerebro; Estados Unidos
Fil: Patil, Dipak N. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Wang, Dandan. Instituto de Investigación Infantil de Seattle. Centro de Investigación Integrativa del Cerebro; Estados Unidos
Fil: Birnbaumer, Lutz. Instituto Nacional de Ciencias de la Salud Ambiental. Laboratorio de neurobiología; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Blakely, Randy D. Universidad Atlántica de Florida. Facultad de Medicina. Departamento de Ciencias Biomédicas e Instituto del Cerebro; Estados Unidos
Fil: Grill, Brock. Instituto de Investigación Infantil de Seattle. Centro de Investigación Integrativa del Cerebro; Estados Unidos
Fil: Grill, Brock. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Fil: Grill, Brock. Universidad de Washington; Estados Unidos
Fil: Martemyanov, Kirill A. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
Abstract: The G protein alpha subunit o (Gao) is one of the most abundant proteins in the nervous system, and pathogenic mutations in its gene (GNAO1) cause movement disorder. However, the function of Gao is ill defined mechanistically. Here, we show that Gao dictates neuromodulatory responsiveness of striatal neurons and is required for movement control. Using in vivo optical sensors and enzymatic assays, we determine that Gao provides a separate transduction channel that modulates coupling of both inhibitory and stimulatory dopamine receptors to the cyclic AMP (cAMP)-generating enzyme adenylyl cyclase. Through a combination of cell-based assays and rodent models, we demonstrate that GNAO1-associated mutations alter Gao function in a neuron-type-specific fashion via a combination of a dominant-negative and loss-of-function mechanisms. Overall, our findings suggest thatGao and its pathological variants function in specific circuits to regulate neuromodulatory signals essential for executing motor programs.
description Fil: Muntean, Brian S. Instituto de Investigación Scripps. Departamento de Neurociencia; Estados Unidos
publishDate 2021
dc.date.none.fl_str_mv 2021
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 https://repositorio.uca.edu.ar/handle/123456789/11617
2211-1247 (on line)
10.1016/j.celrep.2021.108718ll
33535037
Muntean, B., et al. Gao is a major determinant of cAMP signaling in the pathophysiology of movement disorders [en línea]. Cell Reports. 2021, 34. doi: 10.1016/j.celrep.2021.108718ll. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/11617
url https://repositorio.uca.edu.ar/handle/123456789/11617
identifier_str_mv 2211-1247 (on line)
10.1016/j.celrep.2021.108718ll
33535037
Muntean, B., et al. Gao is a major determinant of cAMP signaling in the pathophysiology of movement disorders [en línea]. Cell Reports. 2021, 34. doi: 10.1016/j.celrep.2021.108718ll. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/11617
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Cell Reports. 2021, 34
reponame:Repositorio Institucional (UCA)
instname:Pontificia Universidad Católica Argentina
reponame_str Repositorio Institucional (UCA)
collection Repositorio Institucional (UCA)
instname_str Pontificia Universidad Católica Argentina
repository.name.fl_str_mv Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina
repository.mail.fl_str_mv claudia_fernandez@uca.edu.ar
_version_ 1836638355564003328
score 13.070432

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