論文

基本情報

氏名 日野 真一郎
氏名(カナ) ヒノ シンイチロウ
氏名(英語) HINO SHINICHIROU
所属 中村学園大学 栄養科学部 栄養科学科
職名 教授

題名

Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis

単著・共著の別

著者

(The first two authors contributed equally) Hino S-I
Saito A
Murakami T
Kanemoto S
Kondo S
Saitoh M
Nishimura R
Yoneda T
Furuichi T
Ikegawa S
Ikawa M
Okabe M
Imaizumi K

担当区分

概要

Many tissues have a specific signal transduction system for endoplasmic reticulum (ER) dysfunction; however, the mechanisms underlying the ER stress response in cartilage remain unclear. BBF2H7 (BBF2 human homologue on chromosome 7), an ER-resident basic leucine zipper transcription factor, is activated in response to ER stress(1) and is highly expressed in chondrocytes. In this study, we generated Bbf2h7(-/-) ice to assess the in vivo function of BBF2H7. The mice showed severe chondrodysplasia and died by suffocation shortly after birth because of an immature chest cavity. The cartilage showed a lack of typical columnar structure in the proliferating zone and a decrease in the size of the hypertrophic zone, resulting in a significant reduction of extracellular matrix proteins. Interestingly, proliferating chondrocytes showed abnormally expanded ER, containing aggregated type II collagen (Col2) and cartilage oligomeric matrix protein (COMP). We identified Sec23a, which encodes a coat protein complex II component responsible for protein transport from the ER to the Golgi(2,3), as a target of BBF2H7, which directly bound to a CRE-like sequence in the promoter region of Sec23a to activate its transcription. When Sec23a was introduced to Bbf2h7(-/-) chondrocytes, the impaired transport and secretion of cartilage matrix proteins was totally restored, indicating that by activating protein secretion the BBF2H7-Sec23a pathway has a crucial role in chondrogenesis. Our findings provide a new link by which ER stress is converted to signalling for the activation of ER-to-Golgi trafficking.

発表雑誌等の名称

Nature Cell Biology

出版者

NATURE PUBLISHING GROUP

11

10

開始ページ

1197

終了ページ

1204

発行又は発表の年月

2009/10

査読の有無

有り

招待の有無

無し

記述言語

英語

掲載種別

研究論文(学術雑誌)

国際・国内誌

国際誌

国際共著

ISSN

eISSN

DOI

10.1038/ncb1962

Cinii Articles ID

Cinii Books ID

Pubmed ID

PubMed Central 記事ID

形式

無償ダウンロード

JGlobalID

arXiv ID

ORCIDのPut Code

DBLP ID