Binding of galectin-1 to αIIbβ3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis

Autores
Romaniuk, María Albertina; Croci Russo, Diego Omar; Lapponi, María José; Tribulatti, María Virginia; Negrotto, Soledad; Poirier, Francoise; Campetella, Oscar Eduardo; Rabinovich, Gabriel Adrián; Schattner, Mirta Ana
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Understanding noncanonical mechanisms of platelet activation represents an important challenge for the identification of novel therapeutic targets in bleeding disorders, thrombosis, and cancer. We previously reported that galectin-1 (Gal-1), a β-galactosidebinding protein, triggers platelet activation in vitro. Here we investigated the molecular mechanisms underlying this function and the physiological relevance of endogenous Gal-1 in hemostasis. Mass spectrometry analysis, as well as studies using blocking antibodies against the anti-αIIbsubunit ofαIIbβ 3 integrin or platelets from patients with Glanzmann's thrombasthenia syndrome (αIIbβ3 deficiency), identified this integrin as a functional Gal-1 receptor in platelets. Binding of Gal-1 to platelets triggered the phosphorylation of β3-integrin, Syk, MAPKs, PI3K, PLCγ2, thromboxane (TXA2) release, and Ca 2+mobilization. Not only soluble but also immobilized Gal-1 promoted platelet activation. Gal-1-deficient (Lgals1-/-) mice showed increased bleeding time (P<0.0002, knockout vs. wild type), which was not associated with an abnormal platelet count. Lgals1-/- platelets exhibited normal aggregation to PAR4, ADP, arachidonic acid, or collagen but abnormal ATP release at low collagen concentrations. Impaired spreading on fibrinogen and clot retraction with normal levels of αIIbβ 3 was also observed in Lgals1-/- platelets, indicating a failure in the "outsidein"signaling through this integrin. This study identifies a noncanonical mechanism, based on galectin-integrin interactions, for regulating platelet activation. © FASEB.
Fil: Romaniuk, María Albertina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Lapponi, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Tribulatti, María Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Poirier, Francoise. Centre National de la Recherche Scientifique; Francia. Paris Diderot University; Francia
Fil: Campetella, Oscar Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
Glycobiology
Inflammation
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:11336/52943
Acceder
id CONICETDig_81ce415f31096b56ca00ad17d6deb1d3
oai_identifier_str oai:ri.conicet.gov.ar:11336/52943
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Binding of galectin-1 to αIIbβ3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasisRomaniuk, María AlbertinaCroci Russo, Diego OmarLapponi, María JoséTribulatti, María VirginiaNegrotto, SoledadPoirier, FrancoiseCampetella, Oscar EduardoRabinovich, Gabriel AdriánSchattner, Mirta AnaGlycobiologyInflammationhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Understanding noncanonical mechanisms of platelet activation represents an important challenge for the identification of novel therapeutic targets in bleeding disorders, thrombosis, and cancer. We previously reported that galectin-1 (Gal-1), a β-galactosidebinding protein, triggers platelet activation in vitro. Here we investigated the molecular mechanisms underlying this function and the physiological relevance of endogenous Gal-1 in hemostasis. Mass spectrometry analysis, as well as studies using blocking antibodies against the anti-αIIbsubunit ofαIIbβ 3 integrin or platelets from patients with Glanzmann's thrombasthenia syndrome (αIIbβ3 deficiency), identified this integrin as a functional Gal-1 receptor in platelets. Binding of Gal-1 to platelets triggered the phosphorylation of β3-integrin, Syk, MAPKs, PI3K, PLCγ2, thromboxane (TXA2) release, and Ca 2+mobilization. Not only soluble but also immobilized Gal-1 promoted platelet activation. Gal-1-deficient (Lgals1-/-) mice showed increased bleeding time (P<0.0002, knockout vs. wild type), which was not associated with an abnormal platelet count. Lgals1-/- platelets exhibited normal aggregation to PAR4, ADP, arachidonic acid, or collagen but abnormal ATP release at low collagen concentrations. Impaired spreading on fibrinogen and clot retraction with normal levels of αIIbβ 3 was also observed in Lgals1-/- platelets, indicating a failure in the "outsidein"signaling through this integrin. This study identifies a noncanonical mechanism, based on galectin-integrin interactions, for regulating platelet activation. © FASEB.Fil: Romaniuk, María Albertina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Lapponi, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Tribulatti, María Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Poirier, Francoise. Centre National de la Recherche Scientifique; Francia. Paris Diderot University; FranciaFil: Campetella, Oscar Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFederation of American Societies for Experimental Biology2012-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/52943Romaniuk, María Albertina; Croci Russo, Diego Omar; Lapponi, María José; Tribulatti, María Virginia; Negrotto, Soledad; et al.; Binding of galectin-1 to αIIbβ3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis; Federation of American Societies for Experimental Biology; FASEB Journal; 26; 7; 7-2012; 2788-27980892-6638CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1096/fj.11-197541info:eu-repo/semantics/altIdentifier/url/https://www.fasebj.org/doi/10.1096/fj.11-197541info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:41:02Zoai:ri.conicet.gov.ar:11336/52943instacron: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 14:41:02.405CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Binding of galectin-1 to αIIbβ3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis
title Binding of galectin-1 to αIIbβ3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis
spellingShingle Binding of galectin-1 to αIIbβ3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis
Romaniuk, María Albertina
Glycobiology
Inflammation
title_short Binding of galectin-1 to αIIbβ3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis
title_full Binding of galectin-1 to αIIbβ3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis
title_fullStr Binding of galectin-1 to αIIbβ3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis
title_full_unstemmed Binding of galectin-1 to αIIbβ3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis
title_sort Binding of galectin-1 to αIIbβ3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis
dc.creator.none.fl_str_mv Romaniuk, María Albertina
Croci Russo, Diego Omar
Lapponi, María José
Tribulatti, María Virginia
Negrotto, Soledad
Poirier, Francoise
Campetella, Oscar Eduardo
Rabinovich, Gabriel Adrián
Schattner, Mirta Ana
author Romaniuk, María Albertina
author_facet Romaniuk, María Albertina
Croci Russo, Diego Omar
Lapponi, María José
Tribulatti, María Virginia
Negrotto, Soledad
Poirier, Francoise
Campetella, Oscar Eduardo
Rabinovich, Gabriel Adrián
Schattner, Mirta Ana
author_role author
author2 Croci Russo, Diego Omar
Lapponi, María José
Tribulatti, María Virginia
Negrotto, Soledad
Poirier, Francoise
Campetella, Oscar Eduardo
Rabinovich, Gabriel Adrián
Schattner, Mirta Ana
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Glycobiology
Inflammation
topic Glycobiology
Inflammation
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Understanding noncanonical mechanisms of platelet activation represents an important challenge for the identification of novel therapeutic targets in bleeding disorders, thrombosis, and cancer. We previously reported that galectin-1 (Gal-1), a β-galactosidebinding protein, triggers platelet activation in vitro. Here we investigated the molecular mechanisms underlying this function and the physiological relevance of endogenous Gal-1 in hemostasis. Mass spectrometry analysis, as well as studies using blocking antibodies against the anti-αIIbsubunit ofαIIbβ 3 integrin or platelets from patients with Glanzmann's thrombasthenia syndrome (αIIbβ3 deficiency), identified this integrin as a functional Gal-1 receptor in platelets. Binding of Gal-1 to platelets triggered the phosphorylation of β3-integrin, Syk, MAPKs, PI3K, PLCγ2, thromboxane (TXA2) release, and Ca 2+mobilization. Not only soluble but also immobilized Gal-1 promoted platelet activation. Gal-1-deficient (Lgals1-/-) mice showed increased bleeding time (P<0.0002, knockout vs. wild type), which was not associated with an abnormal platelet count. Lgals1-/- platelets exhibited normal aggregation to PAR4, ADP, arachidonic acid, or collagen but abnormal ATP release at low collagen concentrations. Impaired spreading on fibrinogen and clot retraction with normal levels of αIIbβ 3 was also observed in Lgals1-/- platelets, indicating a failure in the "outsidein"signaling through this integrin. This study identifies a noncanonical mechanism, based on galectin-integrin interactions, for regulating platelet activation. © FASEB.
Fil: Romaniuk, María Albertina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Lapponi, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Tribulatti, María Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Poirier, Francoise. Centre National de la Recherche Scientifique; Francia. Paris Diderot University; Francia
Fil: Campetella, Oscar Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Understanding noncanonical mechanisms of platelet activation represents an important challenge for the identification of novel therapeutic targets in bleeding disorders, thrombosis, and cancer. We previously reported that galectin-1 (Gal-1), a β-galactosidebinding protein, triggers platelet activation in vitro. Here we investigated the molecular mechanisms underlying this function and the physiological relevance of endogenous Gal-1 in hemostasis. Mass spectrometry analysis, as well as studies using blocking antibodies against the anti-αIIbsubunit ofαIIbβ 3 integrin or platelets from patients with Glanzmann's thrombasthenia syndrome (αIIbβ3 deficiency), identified this integrin as a functional Gal-1 receptor in platelets. Binding of Gal-1 to platelets triggered the phosphorylation of β3-integrin, Syk, MAPKs, PI3K, PLCγ2, thromboxane (TXA2) release, and Ca 2+mobilization. Not only soluble but also immobilized Gal-1 promoted platelet activation. Gal-1-deficient (Lgals1-/-) mice showed increased bleeding time (P<0.0002, knockout vs. wild type), which was not associated with an abnormal platelet count. Lgals1-/- platelets exhibited normal aggregation to PAR4, ADP, arachidonic acid, or collagen but abnormal ATP release at low collagen concentrations. Impaired spreading on fibrinogen and clot retraction with normal levels of αIIbβ 3 was also observed in Lgals1-/- platelets, indicating a failure in the "outsidein"signaling through this integrin. This study identifies a noncanonical mechanism, based on galectin-integrin interactions, for regulating platelet activation. © FASEB.
publishDate 2012
dc.date.none.fl_str_mv 2012-07
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/11336/52943
Romaniuk, María Albertina; Croci Russo, Diego Omar; Lapponi, María José; Tribulatti, María Virginia; Negrotto, Soledad; et al.; Binding of galectin-1 to αIIbβ3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis; Federation of American Societies for Experimental Biology; FASEB Journal; 26; 7; 7-2012; 2788-2798
0892-6638
CONICET Digital
CONICET
url http://hdl.handle.net/11336/52943
identifier_str_mv Romaniuk, María Albertina; Croci Russo, Diego Omar; Lapponi, María José; Tribulatti, María Virginia; Negrotto, Soledad; et al.; Binding of galectin-1 to αIIbβ3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis; Federation of American Societies for Experimental Biology; FASEB Journal; 26; 7; 7-2012; 2788-2798
0892-6638
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1096/fj.11-197541
info:eu-repo/semantics/altIdentifier/url/https://www.fasebj.org/doi/10.1096/fj.11-197541
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 Federation of American Societies for Experimental Biology
publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
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 13.22299

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