Artículos de revistas
The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase β1 subunits
Fecha
2016-01-15Registro en:
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
Autor
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
Resumen
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.