WFS1 protein modulates the free Ca(2+) concentration in the endoplasmic reticulum

FEBS Lett. 2006 Oct 16;580(24):5635-40. doi: 10.1016/j.febslet.2006.09.007. Epub 2006 Sep 15.


The WFS1 gene, encoding an endoplasmic reticulum (ER) membrane glycoprotein, is mutated in Wolfram syndrome characterized by diabetes mellitus and optic atrophy. Herein, Ca(2+) dynamics were examined in WFS1-knockdown and -overexpressing HEK293 cells. Studies using ER-targeted Ca(2+)-sensitive photoprotein aequorin demonstrated WFS1 protein to positively modulate ER Ca(2+) levels by increasing the rate of Ca(2+) uptake. Furthermore, Ca(2+) imaging with Fura-2 showed the magnitude of the store-operated Ca(2+) entry to parallel WFS1 expression levels. These data indicate that WFS1 protein participates in the regulation of cellular Ca(2+) homeostasis, at least partly, by modulating the filling state of the ER Ca(2+) store.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Calcium / metabolism*
  • Cell Line
  • Endoplasmic Reticulum / metabolism*
  • Gene Expression Regulation
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • RNA Interference


  • Membrane Proteins
  • wolframin protein
  • Calcium