Binding of galectin‐1 to α IIb β 3 integrin triggers “outside‐in” signals, stimulates platelet activation, and controls primary hemostasis

Autores
Romaniuk, Maria Albertina; Croci Russo, Diego Omar; Lapponi, Maria Jose; Tribulatti, Maria 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-galactoside-binding 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-αIIb subunit of αIIbβ3 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 Ca2+ 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 αIIbβ3 was also observed in Lgals1–/– platelets, indicating a failure in the “outside-in” signaling through this integrin. This study identifies a noncanonical mechanism, based on galectin-integrin interactions, for regulating platelet activation.—Romaniuk, M. A., Croci, D. O., Lapponi, M. J., Tribulatti, M. V., Negrotto, S., Poirier, F., Campetella, O., Rabinovich, G. A., Schattner, M. Binding of galectin-1 to αIIbβ3 integrin triggers “outside-in” signals, stimulates platelet activation, and controls primary hemostasis. FASEB J. 26, 2788–2798 (2012). www.fasebj.org
Fil: Romaniuk, Maria 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 Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lapponi, Maria Jose. 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, Maria 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
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
HEMOSTASIS
GALECTIN
INTEGRIN BINDING
PLATELET ACTIVATION
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:11336/272419
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Binding of galectin‐1 to α IIb β 3 integrin triggers “outside‐in” signals, stimulates platelet activation, and controls primary hemostasisRomaniuk, Maria AlbertinaCroci Russo, Diego OmarLapponi, Maria JoseTribulatti, Maria VirginiaNegrotto, SoledadPoirier, FrancoiseCampetella, Oscar EduardoRabinovich, Gabriel AdriánSchattner, Mirta AnaHEMOSTASISGALECTININTEGRIN BINDINGPLATELET ACTIVATIONhttps://purl.org/becyt/ford/3.1https://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-galactoside-binding 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-αIIb subunit of αIIbβ3 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 Ca2+ 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 αIIbβ3 was also observed in Lgals1–/– platelets, indicating a failure in the “outside-in” signaling through this integrin. This study identifies a noncanonical mechanism, based on galectin-integrin interactions, for regulating platelet activation.—Romaniuk, M. A., Croci, D. O., Lapponi, M. J., Tribulatti, M. V., Negrotto, S., Poirier, F., Campetella, O., Rabinovich, G. A., Schattner, M. Binding of galectin-1 to αIIbβ3 integrin triggers “outside-in” signals, stimulates platelet activation, and controls primary hemostasis. FASEB J. 26, 2788–2798 (2012). www.fasebj.orgFil: Romaniuk, Maria 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 Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lapponi, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Tribulatti, Maria 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; 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/11336/272419Romaniuk, Maria Albertina; Croci Russo, Diego Omar; Lapponi, Maria Jose; Tribulatti, Maria Virginia; Negrotto, Soledad; et al.; Binding of galectin‐1 to α IIb β 3 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/url/https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.11-197541info:eu-repo/semantics/altIdentifier/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 Técnicas2025-10-15T14:24:27Zoai:ri.conicet.gov.ar:11336/272419instacron: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 14:24:27.548CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Binding of galectin‐1 to α IIb β 3 integrin triggers “outside‐in” signals, stimulates platelet activation, and controls primary hemostasis
title Binding of galectin‐1 to α IIb β 3 integrin triggers “outside‐in” signals, stimulates platelet activation, and controls primary hemostasis
spellingShingle Binding of galectin‐1 to α IIb β 3 integrin triggers “outside‐in” signals, stimulates platelet activation, and controls primary hemostasis
Romaniuk, Maria Albertina
HEMOSTASIS
GALECTIN
INTEGRIN BINDING
PLATELET ACTIVATION
title_short Binding of galectin‐1 to α IIb β 3 integrin triggers “outside‐in” signals, stimulates platelet activation, and controls primary hemostasis
title_full Binding of galectin‐1 to α IIb β 3 integrin triggers “outside‐in” signals, stimulates platelet activation, and controls primary hemostasis
title_fullStr Binding of galectin‐1 to α IIb β 3 integrin triggers “outside‐in” signals, stimulates platelet activation, and controls primary hemostasis
title_full_unstemmed Binding of galectin‐1 to α IIb β 3 integrin triggers “outside‐in” signals, stimulates platelet activation, and controls primary hemostasis
title_sort Binding of galectin‐1 to α IIb β 3 integrin triggers “outside‐in” signals, stimulates platelet activation, and controls primary hemostasis
dc.creator.none.fl_str_mv Romaniuk, Maria Albertina
Croci Russo, Diego Omar
Lapponi, Maria Jose
Tribulatti, Maria Virginia
Negrotto, Soledad
Poirier, Francoise
Campetella, Oscar Eduardo
Rabinovich, Gabriel Adrián
Schattner, Mirta Ana
author Romaniuk, Maria Albertina
author_facet Romaniuk, Maria Albertina
Croci Russo, Diego Omar
Lapponi, Maria Jose
Tribulatti, Maria Virginia
Negrotto, Soledad
Poirier, Francoise
Campetella, Oscar Eduardo
Rabinovich, Gabriel Adrián
Schattner, Mirta Ana
author_role author
author2 Croci Russo, Diego Omar
Lapponi, Maria Jose
Tribulatti, Maria 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 HEMOSTASIS
GALECTIN
INTEGRIN BINDING
PLATELET ACTIVATION
topic HEMOSTASIS
GALECTIN
INTEGRIN BINDING
PLATELET ACTIVATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
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-galactoside-binding 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-αIIb subunit of αIIbβ3 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 Ca2+ 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 αIIbβ3 was also observed in Lgals1–/– platelets, indicating a failure in the “outside-in” signaling through this integrin. This study identifies a noncanonical mechanism, based on galectin-integrin interactions, for regulating platelet activation.—Romaniuk, M. A., Croci, D. O., Lapponi, M. J., Tribulatti, M. V., Negrotto, S., Poirier, F., Campetella, O., Rabinovich, G. A., Schattner, M. Binding of galectin-1 to αIIbβ3 integrin triggers “outside-in” signals, stimulates platelet activation, and controls primary hemostasis. FASEB J. 26, 2788–2798 (2012). www.fasebj.org
Fil: Romaniuk, Maria 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 Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lapponi, Maria Jose. 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, Maria 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
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-galactoside-binding 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-αIIb subunit of αIIbβ3 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 Ca2+ 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 αIIbβ3 was also observed in Lgals1–/– platelets, indicating a failure in the “outside-in” signaling through this integrin. This study identifies a noncanonical mechanism, based on galectin-integrin interactions, for regulating platelet activation.—Romaniuk, M. A., Croci, D. O., Lapponi, M. J., Tribulatti, M. V., Negrotto, S., Poirier, F., Campetella, O., Rabinovich, G. A., Schattner, M. Binding of galectin-1 to αIIbβ3 integrin triggers “outside-in” signals, stimulates platelet activation, and controls primary hemostasis. FASEB J. 26, 2788–2798 (2012). www.fasebj.org
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
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/272419
Romaniuk, Maria Albertina; Croci Russo, Diego Omar; Lapponi, Maria Jose; Tribulatti, Maria Virginia; Negrotto, Soledad; et al.; Binding of galectin‐1 to α IIb β 3 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/11336/272419
identifier_str_mv Romaniuk, Maria Albertina; Croci Russo, Diego Omar; Lapponi, Maria Jose; Tribulatti, Maria Virginia; Negrotto, Soledad; et al.; Binding of galectin‐1 to α IIb β 3 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/url/https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.11-197541
info:eu-repo/semantics/altIdentifier/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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