Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channels

Autores
Gonzalez, Laura Elisabeth; Kotler, Monica Lidia; Vattino, Lucas Gabriel; Conti, Eugenia; Reisin, Ricardo C.; Mulatz, Kirk J.; Snutch, Terrance P.; Uchitel, Osvaldo Daniel
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a gradual loss of motoneurons. The majority of ALS cases are associated with a sporadic form whose etiology is unknown. Several pieces of evidence favor autoimmunity as a potential contributor to sporadic ALS pathology. To gain understanding concerning possible antigens interacting with IgGs from sporadic ALS patients (ALS-IgGs), we studied immunoreactivity against neuromuscular junction (NMJ), spinal cord and cerebellum of mice with and without the Ca V2.1 pore-forming subunit of the P/Q-type voltage-gated calcium (Ca 2+) channel. ALS-IgGs showed a strong reactivity against NMJs of wild-type diaphragms. ALS-IgGs also increased muscle miniature end-plate potential frequency, suggesting a functional role for ALS-IgGs on synaptic signaling. In support, in mice lacking the Ca V2.1 subunit ALS-IgGs showed significantly reduced NMJ immunoreactivity and did not alter spontaneous acetylcholine release. This difference in reactivity was absent when comparing N-type Ca 2+ channel wild-type or null mice. These results are particularly relevant because motoneurons are known to be early pathogenic targets in ALS. Our findings add further evidence supporting autoimmunity as one of the possible mechanisms contributing to ALS pathology. They also suggest that serum autoantibodies in a subset of ALS patients would interact with NMJ proteins down-regulated when P/Q-type channels are absent. © 2011 International Society for Neurochemistry.
Fil: Gonzalez, Laura Elisabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Kotler, Monica Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Vattino, Lucas Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Conti, Eugenia. Hospital Británico de Buenos Aires; Argentina
Fil: Reisin, Ricardo C.. Hospital Británico de Buenos Aires; Argentina
Fil: Mulatz, Kirk J.. University of British Columbia; Canadá
Fil: Snutch, Terrance P.. University of British Columbia; Canadá
Fil: Uchitel, Osvaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Materia
Amyotrophic Lateral Sclerosis
Autoantibodies
Autoimmunity
Calcium Channels
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:11336/65720
Acceder
id CONICETDig_f3c7a53deb7768ccbe2f2425961aec34
oai_identifier_str oai:ri.conicet.gov.ar:11336/65720
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channelsGonzalez, Laura ElisabethKotler, Monica LidiaVattino, Lucas GabrielConti, EugeniaReisin, Ricardo C.Mulatz, Kirk J.Snutch, Terrance P.Uchitel, Osvaldo DanielAmyotrophic Lateral SclerosisAutoantibodiesAutoimmunityCalcium Channelshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a gradual loss of motoneurons. The majority of ALS cases are associated with a sporadic form whose etiology is unknown. Several pieces of evidence favor autoimmunity as a potential contributor to sporadic ALS pathology. To gain understanding concerning possible antigens interacting with IgGs from sporadic ALS patients (ALS-IgGs), we studied immunoreactivity against neuromuscular junction (NMJ), spinal cord and cerebellum of mice with and without the Ca V2.1 pore-forming subunit of the P/Q-type voltage-gated calcium (Ca 2+) channel. ALS-IgGs showed a strong reactivity against NMJs of wild-type diaphragms. ALS-IgGs also increased muscle miniature end-plate potential frequency, suggesting a functional role for ALS-IgGs on synaptic signaling. In support, in mice lacking the Ca V2.1 subunit ALS-IgGs showed significantly reduced NMJ immunoreactivity and did not alter spontaneous acetylcholine release. This difference in reactivity was absent when comparing N-type Ca 2+ channel wild-type or null mice. These results are particularly relevant because motoneurons are known to be early pathogenic targets in ALS. Our findings add further evidence supporting autoimmunity as one of the possible mechanisms contributing to ALS pathology. They also suggest that serum autoantibodies in a subset of ALS patients would interact with NMJ proteins down-regulated when P/Q-type channels are absent. © 2011 International Society for Neurochemistry.Fil: Gonzalez, Laura Elisabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Kotler, Monica Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Vattino, Lucas Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Conti, Eugenia. Hospital Británico de Buenos Aires; ArgentinaFil: Reisin, Ricardo C.. Hospital Británico de Buenos Aires; ArgentinaFil: Mulatz, Kirk J.. University of British Columbia; CanadáFil: Snutch, Terrance P.. University of British Columbia; CanadáFil: Uchitel, Osvaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaWiley Blackwell Publishing, Inc2011-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/65720Gonzalez, Laura Elisabeth; Kotler, Monica Lidia; Vattino, Lucas Gabriel; Conti, Eugenia; Reisin, Ricardo C.; et al.; Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channels; Wiley Blackwell Publishing, Inc; Journal of Neurochemistry; 119; 4; 11-2011; 826-8380022-3042CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1471-4159.2011.07462.xinfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1111/j.1471-4159.2011.07462.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:02:51Zoai:ri.conicet.gov.ar:11336/65720instacron: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:34982025-09-10 13:02:51.294CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channels
title Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channels
spellingShingle Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channels
Gonzalez, Laura Elisabeth
Amyotrophic Lateral Sclerosis
Autoantibodies
Autoimmunity
Calcium Channels
title_short Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channels
title_full Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channels
title_fullStr Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channels
title_full_unstemmed Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channels
title_sort Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channels
dc.creator.none.fl_str_mv Gonzalez, Laura Elisabeth
Kotler, Monica Lidia
Vattino, Lucas Gabriel
Conti, Eugenia
Reisin, Ricardo C.
Mulatz, Kirk J.
Snutch, Terrance P.
Uchitel, Osvaldo Daniel
author Gonzalez, Laura Elisabeth
author_facet Gonzalez, Laura Elisabeth
Kotler, Monica Lidia
Vattino, Lucas Gabriel
Conti, Eugenia
Reisin, Ricardo C.
Mulatz, Kirk J.
Snutch, Terrance P.
Uchitel, Osvaldo Daniel
author_role author
author2 Kotler, Monica Lidia
Vattino, Lucas Gabriel
Conti, Eugenia
Reisin, Ricardo C.
Mulatz, Kirk J.
Snutch, Terrance P.
Uchitel, Osvaldo Daniel
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Amyotrophic Lateral Sclerosis
Autoantibodies
Autoimmunity
Calcium Channels
topic Amyotrophic Lateral Sclerosis
Autoantibodies
Autoimmunity
Calcium Channels
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a gradual loss of motoneurons. The majority of ALS cases are associated with a sporadic form whose etiology is unknown. Several pieces of evidence favor autoimmunity as a potential contributor to sporadic ALS pathology. To gain understanding concerning possible antigens interacting with IgGs from sporadic ALS patients (ALS-IgGs), we studied immunoreactivity against neuromuscular junction (NMJ), spinal cord and cerebellum of mice with and without the Ca V2.1 pore-forming subunit of the P/Q-type voltage-gated calcium (Ca 2+) channel. ALS-IgGs showed a strong reactivity against NMJs of wild-type diaphragms. ALS-IgGs also increased muscle miniature end-plate potential frequency, suggesting a functional role for ALS-IgGs on synaptic signaling. In support, in mice lacking the Ca V2.1 subunit ALS-IgGs showed significantly reduced NMJ immunoreactivity and did not alter spontaneous acetylcholine release. This difference in reactivity was absent when comparing N-type Ca 2+ channel wild-type or null mice. These results are particularly relevant because motoneurons are known to be early pathogenic targets in ALS. Our findings add further evidence supporting autoimmunity as one of the possible mechanisms contributing to ALS pathology. They also suggest that serum autoantibodies in a subset of ALS patients would interact with NMJ proteins down-regulated when P/Q-type channels are absent. © 2011 International Society for Neurochemistry.
Fil: Gonzalez, Laura Elisabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Kotler, Monica Lidia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Vattino, Lucas Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Conti, Eugenia. Hospital Británico de Buenos Aires; Argentina
Fil: Reisin, Ricardo C.. Hospital Británico de Buenos Aires; Argentina
Fil: Mulatz, Kirk J.. University of British Columbia; Canadá
Fil: Snutch, Terrance P.. University of British Columbia; Canadá
Fil: Uchitel, Osvaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
description Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a gradual loss of motoneurons. The majority of ALS cases are associated with a sporadic form whose etiology is unknown. Several pieces of evidence favor autoimmunity as a potential contributor to sporadic ALS pathology. To gain understanding concerning possible antigens interacting with IgGs from sporadic ALS patients (ALS-IgGs), we studied immunoreactivity against neuromuscular junction (NMJ), spinal cord and cerebellum of mice with and without the Ca V2.1 pore-forming subunit of the P/Q-type voltage-gated calcium (Ca 2+) channel. ALS-IgGs showed a strong reactivity against NMJs of wild-type diaphragms. ALS-IgGs also increased muscle miniature end-plate potential frequency, suggesting a functional role for ALS-IgGs on synaptic signaling. In support, in mice lacking the Ca V2.1 subunit ALS-IgGs showed significantly reduced NMJ immunoreactivity and did not alter spontaneous acetylcholine release. This difference in reactivity was absent when comparing N-type Ca 2+ channel wild-type or null mice. These results are particularly relevant because motoneurons are known to be early pathogenic targets in ALS. Our findings add further evidence supporting autoimmunity as one of the possible mechanisms contributing to ALS pathology. They also suggest that serum autoantibodies in a subset of ALS patients would interact with NMJ proteins down-regulated when P/Q-type channels are absent. © 2011 International Society for Neurochemistry.
publishDate 2011
dc.date.none.fl_str_mv 2011-11
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/11336/65720
Gonzalez, Laura Elisabeth; Kotler, Monica Lidia; Vattino, Lucas Gabriel; Conti, Eugenia; Reisin, Ricardo C.; et al.; Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channels; Wiley Blackwell Publishing, Inc; Journal of Neurochemistry; 119; 4; 11-2011; 826-838
0022-3042
CONICET Digital
CONICET
url http://hdl.handle.net/11336/65720
identifier_str_mv Gonzalez, Laura Elisabeth; Kotler, Monica Lidia; Vattino, Lucas Gabriel; Conti, Eugenia; Reisin, Ricardo C.; et al.; Amyotrophic lateral sclerosis-immunoglobulins selectively interact with neuromuscular junctions expressing P/Q-type calcium channels; Wiley Blackwell Publishing, Inc; Journal of Neurochemistry; 119; 4; 11-2011; 826-838
0022-3042
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1471-4159.2011.07462.x
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1111/j.1471-4159.2011.07462.x
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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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
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, 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 12.993085

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