Modulation of Cell Polarization by the Na+-K+-ATPase-associated Protein FXYD5 (Dysadherin)

Am J Physiol Cell Physiol. 2014 Jun 1;306(11):C1080-8. doi: 10.1152/ajpcell.00042.2014. Epub 2014 Apr 9.

Abstract

FXYD5 (dysadherin or also called a related to ion channel, RIC) is a transmembrane auxiliary subunit of the Na(+)-K(+)-ATPase shown to increase its maximal velocity (Vmax). FXYD5 has also been identified as a cancer-associated protein whose expression in tumor-derived cell lines impairs cytoskeletal organization and increases cell motility. Previously, we have demonstrated that the expression of FXYD5 in M1 cells derived from mouse kidney collecting duct impairs the formation of tight and adherence junctions. The current study aimed to further explore effects of FXYD5 at a single cell level. It was found that in M1, as well as three other cell lines, FXYD5 inhibits transformation of adhered single cells from the initial radial shape to a flattened, elongated shape in the first stage of monolayer formation. This is also correlated to less ordered actin cables and fewer focal points. Structure-function analysis has demonstrated that the transmembrane domain of FXYD5, and not its unique extracellular segment, mediates the inhibition of change in cell shape. This domain has been shown before to be involved in the association of FXYD5 with the Na(+)-K(+)-ATPase, which leads to the increase in Vmax. Furthermore, specific transmembrane point mutations in FXYD5 that either increase or decrease its effect on cell elongation had a corresponding effect on the coimmunoprecipitation of FXYD5 with α Na(+)-K(+)-ATPase. These findings lend support to the possibility that FXYD5 affects cell polarization through its transmembrane domain interaction with the Na(+)-K(+)-ATPase. Yet interaction of FXYD5 with other proteins cannot be excluded.

Keywords: FXYD5; Na+-K+-ATPase; anterior-posterior polarity; cell adhesion; dysadherin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cell Polarity / physiology*
  • HEK293 Cells
  • Humans
  • Kidney Tubules, Collecting / cytology
  • Kidney Tubules, Collecting / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Sodium-Potassium-Exchanging ATPase / physiology*

Substances

  • FXYD5 protein, mouse
  • Membrane Proteins
  • Sodium-Potassium-Exchanging ATPase