The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits

Autores
Tokhtaeva, Elmira; Sun, Haying; Deiss Yehiely, Nimrod; Wen, Yi; Soni, Pritin N.; Gabrielli, Nieves María; Marcus, Elizabeth A.; Ridge, Karen M.; Sachs, George; Vazquez, Monica Hebe; Sznajder, Jacob I.; Vagin, Olga; Dada, Laura Andrea
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
FXYD5 (also known as dysadherin), a regulatory subunit of the Na,K-ATPase, impairs intercellular adhesion by a poorly understood mechanism. Here, we determined whether FXYD5 disrupts the trans-dimerization of Na,K-ATPase molecules located in neighboring cells. Mutagenesis of the Na,K-ATPase β1 subunit identified four conserved residues, including Y199, that are crucial for the intercellular Na,K-ATPase trans-dimerization and adhesion. Modulation of expression of FXYD5 or of the β1 subunit with intact or mutated β1?β1 binding sites demonstrated that the anti-adhesive effect of FXYD5 depends on the presence of Y199 in the β1 subunit. Immunodetection of the plasma membrane FXYD5 was prevented by the presence of O-glycans. Partial FXYD5 deglycosylation enabled antibody binding and showed that the protein level and the degree of O-glycosylation were greater in cancer than in normal cells. FXYD5-induced impairment of adhesion was abolished by both genetic and pharmacological inhibition of FXYD5 O-glycosylation. Therefore, the extracellular O-glycosylated domain of FXYD5 impairs adhesion by interfering with intercellular β1?β1 interactions, suggesting that the ratio between FXYD5 and α1?β1 heterodimer determines whether the Na,K-ATPase acts as a positive or negative regulator of intercellular adhesion.
Fil: Tokhtaeva, Elmira. University of California at Los Angeles; Estados Unidos
Fil: Sun, Haying. Northwestern University; Estados Unidos
Fil: Deiss Yehiely, Nimrod. Northwestern University; Estados Unidos
Fil: Wen, Yi. University of California at Los Angeles; Estados Unidos
Fil: Soni, Pritin N.. Northwestern University; Estados Unidos
Fil: Gabrielli, Nieves María. 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. Northwestern University; Estados Unidos
Fil: Marcus, Elizabeth A.. University of California at Los Angeles; Estados Unidos
Fil: Ridge, Karen M.. Northwestern University; Estados Unidos
Fil: Sachs, George. University of California at Los Angeles; Estados Unidos
Fil: Vazquez, Monica Hebe. 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: Sznajder, Jacob I.. Northwestern University; Estados Unidos
Fil: Vagin, Olga. University of California at Los Angeles; Estados Unidos
Fil: Dada, Laura Andrea. Northwestern University; Estados Unidos
Materia
CELL ADHESION
GLYCOSYLATION
FXYD5
NaK ATPAse
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:11336/23035
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/23035
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunitsTokhtaeva, ElmiraSun, HayingDeiss Yehiely, NimrodWen, YiSoni, Pritin N.Gabrielli, Nieves MaríaMarcus, Elizabeth A.Ridge, Karen M.Sachs, GeorgeVazquez, Monica HebeSznajder, Jacob I.Vagin, OlgaDada, Laura AndreaCELL ADHESIONGLYCOSYLATIONFXYD5NaK ATPAsehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1FXYD5 (also known as dysadherin), a regulatory subunit of the Na,K-ATPase, impairs intercellular adhesion by a poorly understood mechanism. Here, we determined whether FXYD5 disrupts the trans-dimerization of Na,K-ATPase molecules located in neighboring cells. Mutagenesis of the Na,K-ATPase β1 subunit identified four conserved residues, including Y199, that are crucial for the intercellular Na,K-ATPase trans-dimerization and adhesion. Modulation of expression of FXYD5 or of the β1 subunit with intact or mutated β1?β1 binding sites demonstrated that the anti-adhesive effect of FXYD5 depends on the presence of Y199 in the β1 subunit. Immunodetection of the plasma membrane FXYD5 was prevented by the presence of O-glycans. Partial FXYD5 deglycosylation enabled antibody binding and showed that the protein level and the degree of O-glycosylation were greater in cancer than in normal cells. FXYD5-induced impairment of adhesion was abolished by both genetic and pharmacological inhibition of FXYD5 O-glycosylation. Therefore, the extracellular O-glycosylated domain of FXYD5 impairs adhesion by interfering with intercellular β1?β1 interactions, suggesting that the ratio between FXYD5 and α1?β1 heterodimer determines whether the Na,K-ATPase acts as a positive or negative regulator of intercellular adhesion.Fil: Tokhtaeva, Elmira. University of California at Los Angeles; Estados UnidosFil: Sun, Haying. Northwestern University; Estados UnidosFil: Deiss Yehiely, Nimrod. Northwestern University; Estados UnidosFil: Wen, Yi. University of California at Los Angeles; Estados UnidosFil: Soni, Pritin N.. Northwestern University; Estados UnidosFil: Gabrielli, Nieves María. 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. Northwestern University; Estados UnidosFil: Marcus, Elizabeth A.. University of California at Los Angeles; Estados UnidosFil: Ridge, Karen M.. Northwestern University; Estados UnidosFil: Sachs, George. University of California at Los Angeles; Estados UnidosFil: Vazquez, Monica Hebe. 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: Sznajder, Jacob I.. Northwestern University; Estados UnidosFil: Vagin, Olga. University of California at Los Angeles; Estados UnidosFil: Dada, Laura Andrea. Northwestern University; Estados UnidosCompany of Biologists2016-01-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/23035Tokhtaeva, Elmira; Sun, Haying; Deiss Yehiely, Nimrod; Wen, Yi; Soni, Pritin N.; et al.; The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits; Company of Biologists; Journal of Cell Science; 129; 12; 15-1-2016; 2394-24060021-95331477-9137CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://jcs.biologists.org/content/129/12/2394.longinfo:eu-repo/semantics/altIdentifier/doi/10.1242/jcs.186148info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920254/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:39:25Zoai:ri.conicet.gov.ar:11336/23035instacron: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:34982025-09-29 10:39:25.479CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits
title The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits
spellingShingle The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits
Tokhtaeva, Elmira
CELL ADHESION
GLYCOSYLATION
FXYD5
NaK ATPAse
title_short The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits
title_full The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits
title_fullStr The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits
title_full_unstemmed The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits
title_sort The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits
dc.creator.none.fl_str_mv Tokhtaeva, Elmira
Sun, Haying
Deiss Yehiely, Nimrod
Wen, Yi
Soni, Pritin N.
Gabrielli, Nieves María
Marcus, Elizabeth A.
Ridge, Karen M.
Sachs, George
Vazquez, Monica Hebe
Sznajder, Jacob I.
Vagin, Olga
Dada, Laura Andrea
author Tokhtaeva, Elmira
author_facet Tokhtaeva, Elmira
Sun, Haying
Deiss Yehiely, Nimrod
Wen, Yi
Soni, Pritin N.
Gabrielli, Nieves María
Marcus, Elizabeth A.
Ridge, Karen M.
Sachs, George
Vazquez, Monica Hebe
Sznajder, Jacob I.
Vagin, Olga
Dada, Laura Andrea
author_role author
author2 Sun, Haying
Deiss Yehiely, Nimrod
Wen, Yi
Soni, Pritin N.
Gabrielli, Nieves María
Marcus, Elizabeth A.
Ridge, Karen M.
Sachs, George
Vazquez, Monica Hebe
Sznajder, Jacob I.
Vagin, Olga
Dada, Laura Andrea
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CELL ADHESION
GLYCOSYLATION
FXYD5
NaK ATPAse
topic CELL ADHESION
GLYCOSYLATION
FXYD5
NaK ATPAse
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv FXYD5 (also known as dysadherin), a regulatory subunit of the Na,K-ATPase, impairs intercellular adhesion by a poorly understood mechanism. Here, we determined whether FXYD5 disrupts the trans-dimerization of Na,K-ATPase molecules located in neighboring cells. Mutagenesis of the Na,K-ATPase β1 subunit identified four conserved residues, including Y199, that are crucial for the intercellular Na,K-ATPase trans-dimerization and adhesion. Modulation of expression of FXYD5 or of the β1 subunit with intact or mutated β1?β1 binding sites demonstrated that the anti-adhesive effect of FXYD5 depends on the presence of Y199 in the β1 subunit. Immunodetection of the plasma membrane FXYD5 was prevented by the presence of O-glycans. Partial FXYD5 deglycosylation enabled antibody binding and showed that the protein level and the degree of O-glycosylation were greater in cancer than in normal cells. FXYD5-induced impairment of adhesion was abolished by both genetic and pharmacological inhibition of FXYD5 O-glycosylation. Therefore, the extracellular O-glycosylated domain of FXYD5 impairs adhesion by interfering with intercellular β1?β1 interactions, suggesting that the ratio between FXYD5 and α1?β1 heterodimer determines whether the Na,K-ATPase acts as a positive or negative regulator of intercellular adhesion.
Fil: Tokhtaeva, Elmira. University of California at Los Angeles; Estados Unidos
Fil: Sun, Haying. Northwestern University; Estados Unidos
Fil: Deiss Yehiely, Nimrod. Northwestern University; Estados Unidos
Fil: Wen, Yi. University of California at Los Angeles; Estados Unidos
Fil: Soni, Pritin N.. Northwestern University; Estados Unidos
Fil: Gabrielli, Nieves María. 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. Northwestern University; Estados Unidos
Fil: Marcus, Elizabeth A.. University of California at Los Angeles; Estados Unidos
Fil: Ridge, Karen M.. Northwestern University; Estados Unidos
Fil: Sachs, George. University of California at Los Angeles; Estados Unidos
Fil: Vazquez, Monica Hebe. 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: Sznajder, Jacob I.. Northwestern University; Estados Unidos
Fil: Vagin, Olga. University of California at Los Angeles; Estados Unidos
Fil: Dada, Laura Andrea. Northwestern University; Estados Unidos
description FXYD5 (also known as dysadherin), a regulatory subunit of the Na,K-ATPase, impairs intercellular adhesion by a poorly understood mechanism. Here, we determined whether FXYD5 disrupts the trans-dimerization of Na,K-ATPase molecules located in neighboring cells. Mutagenesis of the Na,K-ATPase β1 subunit identified four conserved residues, including Y199, that are crucial for the intercellular Na,K-ATPase trans-dimerization and adhesion. Modulation of expression of FXYD5 or of the β1 subunit with intact or mutated β1?β1 binding sites demonstrated that the anti-adhesive effect of FXYD5 depends on the presence of Y199 in the β1 subunit. Immunodetection of the plasma membrane FXYD5 was prevented by the presence of O-glycans. Partial FXYD5 deglycosylation enabled antibody binding and showed that the protein level and the degree of O-glycosylation were greater in cancer than in normal cells. FXYD5-induced impairment of adhesion was abolished by both genetic and pharmacological inhibition of FXYD5 O-glycosylation. Therefore, the extracellular O-glycosylated domain of FXYD5 impairs adhesion by interfering with intercellular β1?β1 interactions, suggesting that the ratio between FXYD5 and α1?β1 heterodimer determines whether the Na,K-ATPase acts as a positive or negative regulator of intercellular adhesion.
publishDate 2016
dc.date.none.fl_str_mv 2016-01-15
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/11336/23035
Tokhtaeva, Elmira; Sun, Haying; Deiss Yehiely, Nimrod; Wen, Yi; Soni, Pritin N.; et al.; The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits; Company of Biologists; Journal of Cell Science; 129; 12; 15-1-2016; 2394-2406
0021-9533
1477-9137
CONICET Digital
CONICET
url http://hdl.handle.net/11336/23035
identifier_str_mv Tokhtaeva, Elmira; Sun, Haying; Deiss Yehiely, Nimrod; Wen, Yi; Soni, Pritin N.; et al.; The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits; Company of Biologists; Journal of Cell Science; 129; 12; 15-1-2016; 2394-2406
0021-9533
1477-9137
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://jcs.biologists.org/content/129/12/2394.long
info:eu-repo/semantics/altIdentifier/doi/10.1242/jcs.186148
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920254/
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 Company of Biologists
publisher.none.fl_str_mv Company of Biologists
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 13.070432

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