| First Author | Tokhtaeva E | Year | 2016 |
| Journal | J Cell Sci | Volume | 129 |
| Issue | 12 | Pages | 2394-406 |
| PubMed ID | 27142834 | Mgi Jnum | J:249572 |
| Mgi Id | MGI:5922637 | Doi | 10.1242/jcs.186148 |
| Citation | Tokhtaeva E, et al. (2016) The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase beta1 subunits. J Cell Sci 129(12):2394-406 |
| abstractText | 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 beta1 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 beta1 subunit with intact or mutated beta1-beta1 binding sites demonstrated that the anti-adhesive effect of FXYD5 depends on the presence of Y199 in the beta1 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 beta1-beta1 interactions, suggesting that the ratio between FXYD5 and alpha1-beta1 heterodimer determines whether the Na,K-ATPase acts as a positive or negative regulator of intercellular adhesion. |
