Activating transcription factor 6α is required for the vasopressin neuron system to maintain water balance under dehydration in male mice

Yoshinori Azuma, Daisuke Hagiwara, Wenjun Lu, Yoshiaki Morishita, Hidetaka Suga, Motomitsu Goto, Ryoichi Banno, Yoshihisa Sugimura, Seiichi Oyadomari, Kazutoshi Mori, Akira Shiota, Naoya Asai, Masahide Takahashi, Yutaka Oiso, Hiroshi Arima

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 ATF6&alpha:-/- 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.

Original languageEnglish
Pages (from-to)4905-4914
Number of pages10
JournalEndocrinology
Volume155
Issue number12
DOIs
Publication statusPublished - 01-12-2014

Fingerprint

Activating Transcription Factor 6
Vasopressins
Dehydration
Arginine Vasopressin
Water Deprivation
Neurons
Water
Neurogenic Diabetes Insipidus
Endoplasmic Reticulum
Urine
Endoplasmic Reticulum-Associated Degradation
Mouse Atf6 protein
Polyuria
Supraoptic Nucleus
Protein Unfolding
Endoplasmic Reticulum Stress
Knockout Mice

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Azuma, Yoshinori ; Hagiwara, Daisuke ; Lu, Wenjun ; Morishita, Yoshiaki ; Suga, Hidetaka ; Goto, Motomitsu ; Banno, Ryoichi ; Sugimura, Yoshihisa ; Oyadomari, Seiichi ; Mori, Kazutoshi ; Shiota, Akira ; Asai, Naoya ; Takahashi, Masahide ; Oiso, Yutaka ; Arima, Hiroshi. / Activating transcription factor 6α is required for the vasopressin neuron system to maintain water balance under dehydration in male mice. In: Endocrinology. 2014 ; Vol. 155, No. 12. pp. 4905-4914.
@article{ff2bb203a5474ca3973048b99a640fcc,
title = "Activating transcription factor 6α is required for the vasopressin neuron system to maintain water balance under dehydration in male mice",
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 ATF6&alpha:-/- 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.",
author = "Yoshinori Azuma and Daisuke Hagiwara and Wenjun Lu and Yoshiaki Morishita and Hidetaka Suga and Motomitsu Goto and Ryoichi Banno and Yoshihisa Sugimura and Seiichi Oyadomari and Kazutoshi Mori and Akira Shiota and Naoya Asai and Masahide Takahashi and Yutaka Oiso and Hiroshi Arima",
year = "2014",
month = "12",
day = "1",
doi = "10.1210/en.2014-1522",
language = "English",
volume = "155",
pages = "4905--4914",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "12",

}

Azuma, Y, Hagiwara, D, Lu, W, Morishita, Y, Suga, H, Goto, M, Banno, R, Sugimura, Y, Oyadomari, S, Mori, K, Shiota, A, Asai, N, Takahashi, M, Oiso, Y & Arima, H 2014, 'Activating transcription factor 6α is required for the vasopressin neuron system to maintain water balance under dehydration in male mice', Endocrinology, vol. 155, no. 12, pp. 4905-4914. https://doi.org/10.1210/en.2014-1522

Activating transcription factor 6α is required for the vasopressin neuron system to maintain water balance under dehydration in male mice. / Azuma, Yoshinori; Hagiwara, Daisuke; Lu, Wenjun; Morishita, Yoshiaki; Suga, Hidetaka; Goto, Motomitsu; Banno, Ryoichi; Sugimura, Yoshihisa; Oyadomari, Seiichi; Mori, Kazutoshi; Shiota, Akira; Asai, Naoya; Takahashi, Masahide; Oiso, Yutaka; Arima, Hiroshi.

In: Endocrinology, Vol. 155, No. 12, 01.12.2014, p. 4905-4914.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Activating transcription factor 6α is required for the vasopressin neuron system to maintain water balance under dehydration in male mice

AU - Azuma, Yoshinori

AU - Hagiwara, Daisuke

AU - Lu, Wenjun

AU - Morishita, Yoshiaki

AU - Suga, Hidetaka

AU - Goto, Motomitsu

AU - Banno, Ryoichi

AU - Sugimura, Yoshihisa

AU - Oyadomari, Seiichi

AU - Mori, Kazutoshi

AU - Shiota, Akira

AU - Asai, Naoya

AU - Takahashi, Masahide

AU - Oiso, Yutaka

AU - Arima, Hiroshi

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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 ATF6&alpha:-/- 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.

AB - 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 ATF6&alpha:-/- 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.

UR - http://www.scopus.com/inward/record.url?scp=84914162833&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84914162833&partnerID=8YFLogxK

U2 - 10.1210/en.2014-1522

DO - 10.1210/en.2014-1522

M3 - Article

C2 - 25203138

AN - SCOPUS:84914162833

VL - 155

SP - 4905

EP - 4914

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 12

ER -