Activating Transcription Factor 6α Is Required for the Vasopressin Neuron System to Maintain Water Balance Under Dehydration in Male Mice

Author:

Azuma Yoshinori1,Hagiwara Daisuke1,Lu Wenjun1,Morishita Yoshiaki1,Suga Hidetaka1,Goto Motomitsu1,Banno Ryoichi1,Sugimura Yoshihisa1,Oyadomari Seiichi2,Mori Kazutoshi3,Shiota Akira4,Asai Naoya5,Takahashi Masahide5,Oiso Yutaka1,Arima Hiroshi1

Affiliation:

1. Departments of Endocrinology and Diabetes (Y.A., D.H., W.L., Y.M., H.S., M.G., R.B., Y.S., Y.O., H.A.) , Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan

2. Institute for Genome Research (S.O.), University of Tokushima, Tokushima 770–8503, Japan

3. Department of Biophysics (K.M.), Graduate School of Science, Kyoto University, Kyoto 606–8502, Japan

4. Institute of Immunology Co., Ltd (A.S.), 1198–4 Iwazo, Utsunomiya 321–0973, Japan

5. Pathology (N.A., M.T.), Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan

Abstract

Activating transcription factor 6α (ATF6α) is a sensor of endoplasmic reticulum (ER) stress and increases the expression of ER chaperones and molecules related to the ER-associated degradation of unfolded/misfolded proteins. In this study, we used ATF6α knockout (ATF6α−/−) mice to clarify the role of ATF6α in the arginine vasopressin (AVP) neuron system. Although urine volumes were not different between ATF6α−/− and wild-type (ATF6α+/+) mice with access to water ad libitum, they were increased in ATF6α−/− mice compared with those in ATF6α+/+ mice under intermittent water deprivation (WD) and accompanied by less urine AVP in ATF6α−/− mice. The mRNA expression of immunoglobulin heavy chain binding protein, an ER chaperone, was significantly increased in the supraoptic nucleus in ATF6α+/+ but not ATF6α−/− mice after WD. Electron microscopic analyses demonstrated that the ER lumen of AVP neurons was more dilated in ATF6α−/− mice than in ATF6α+/+ mice after WD. ATF6α−/− mice that were mated with mice possessing a mutation causing familial neurohypophysial diabetes insipidus (FNDI), which is characterized by progressive polyuria and AVP neuronal loss due to the accumulation of mutant AVP precursor in the ER, manifested increased urine volume under intermittent WD. The aggregate formation in the ER of AVP neurons was further impaired in FNDI/ATF6α−/− mice compared with that in FNDI mice, and AVP neuronal loss was accelerated in FNDI/ATF6α−/− mice under WD. These data suggest that ATF6α is required for the AVP neuron system to maintain water balance under dehydration.

Publisher

The Endocrine Society

Subject

Endocrinology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3