WFS1 protein modulates the free Ca2+ concentration in the endoplasmic reticulum

被引:141
作者
Takei, Daisuke
Ishihara, Hisamitsu
Yamaguchi, Suguru
Yamada, Takahiro
Tamura, Akira
Katagiri, Hideki
Maruyama, Yoshio
Oka, Yoshitomo
机构
[1] Tohoku Univ, Grad Sch Med, Div Mol Metab & Diabet, Aoba Ku, Sendai, Miyagi 9808575, Japan
[2] Tohoku Univ, Grad Sch Med, Div Adv Therapeut Metab Dis, Sendai, Miyagi 9808575, Japan
[3] Tohoku Univ, Grad Sch Med, Dept Physiol, Sendai, Miyagi 9808575, Japan
关键词
Wolfram syndrome; WFS1; endoplasmic reticulum; cellular Ca2+ homeostasis;
D O I
10.1016/j.febslet.2006.09.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The WFS1 gene, encoding an endoplasmic reticulum (ER) membrane glycoprotein, is mutated in Wolfram syndrome characterized by diabetes mellitus and optic atrophy. Herein, Ca2+ dynamics were examined in WFS1-knockdown and -over-expressing HEK293 cells. Studies using ER-targeted Ca2+ -sensitive photoprotein aequorin demonstrated WFS1 protein to positively modulate ER Ca2+ levels by increasing the rate of Ca2+ uptake. Furthermore, Ca2+ imaging with Fura-2 showed the magnitude of the store-operated Ca2+ entry to parallel WFS1 expression levels. These data indicate that WFS1 protein participates in the regulation of cellular Ca2+ homeostasis, at least partly, by modulating the filling state of the ER Ca2+ store. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:5635 / 5640
页数:6
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