Title : Endoplasmic reticulum stress and N-glycosylation modulate expression of
WFS1 protein
Abstract :
- Mutations of the WFS1 gene are responsible for two hereditary diseases, Wolfram syndrome and low frequency sensorineural hearing loss
- The WFS1 protein is a glycoprotein located in the endoplasmic reticulum (ER) membrane but its function is poorly understood
- Herein we show WFS1 mRNA and protein levels in pancreatic islets to be increased with ER-stress inducers, thapsigargin and dithiothreitol
- Another ER-stress inducer, the N-glycosylation inhibitor tunicamycin , also raised WFS1 mRNA but not protein levels
- Site-directed mutagenesis showed both Asn-663 and Asn-748 to be N-glycosylated in mouse WFS1 protein
- The glycosylation-defective WFS1 protein , in which Asn-663 and Asn-748 had been substituted with aspartate, exhibited an increased protein turnover rate
- Consistent with this, the WFS1 protein was more rapidly degraded in the presence of tunicamycin
- These data indicate that ER-stress and N-glycosylation play important roles in WFS1 expression and stability, and also suggest regulatory roles for this protein in ER-stress induced cell death