Endoplasmic reticulum stress and N-glycosylation modulate expression of WFS1 protein

Suguru Yamaguchi; Hisamitsu Ishihara; Akira Tamura; Takahiro Yamada; Rui Takahashi; Daisuke Takei; Hideki Katagiri; Yoshitomo Oka

doi:10.1016/j.bbrc.2004.10.017

Endoplasmic reticulum stress and N-glycosylation modulate expression of WFS1 protein

Suguru Yamaguchi, Hisamitsu Ishihara, Akira Tamura, Takahiro Yamada, Rui Takahashi, Daisuke Takei, Hideki Katagiri, Yoshitomo Oka

MED - Medical Sciences

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

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.

Original language	English
Pages (from-to)	250-256
Number of pages	7
Journal	Biochemical and biophysical research communications
Volume	325
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2004.10.017
Publication status	Published - 2004 Dec 3

Keywords

ER-stress
Low frequency sensorineural hearing loss
N-Glycosylation
WFSI
Wolfram syndrome

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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Endoplasmic reticulum stress and N-glycosylation modulate expression of WFS1 protein. / Yamaguchi, Suguru; Ishihara, Hisamitsu; Tamura, Akira; Yamada, Takahiro; Takahashi, Rui; Takei, Daisuke; Katagiri, Hideki; Oka, Yoshitomo.

In: Biochemical and biophysical research communications, Vol. 325, No. 1, 03.12.2004, p. 250-256.

Research output: Contribution to journal › Article › peer-review

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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.",

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note = "Funding Information: We are grateful to Y. Nagura for her expert technical assistance. This work was supported by a grant from Suzuken Memorial Foundation to H.I. and a Grant-in-Aid for Scientific Research (13204062) to Y.O. from the Ministry of Education, Science, Sports and Culture of Japan.",

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