Reference - Detail
| RRC ID | 37613 |
|---|---|
| Author | Saito A, Hino S, Murakami T, Kanemoto S, Kondo S, Saitoh M, Nishimura R, Yoneda T, Furuichi T, Ikegawa S, Ikawa M, Okabe M, Imaizumi K. |
| Title | Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis. |
| Journal | Nat Cell Biol |
| Abstract |
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 and is highly expressed in chondrocytes. In this study, we generated Bbf2h7(-/-) mice 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, 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. |
| Volume | 11(10) |
| Pages | 1197-204 |
| Published | 2009-10-1 |
| DOI | 10.1038/ncb1962 |
| PII | ncb1962 |
| PMID | 19767744 |
| MeSH | Animals Basic-Leucine Zipper Transcription Factors / metabolism* Cartilage Oligomeric Matrix Protein Cartilage, Articular / cytology Cells, Cultured Chondrocytes / physiology Chondrocytes / ultrastructure Chondrogenesis* Collagen Type II / metabolism Embryo, Mammalian Endoplasmic Reticulum / physiology* Endoplasmic Reticulum / ultrastructure Extracellular Matrix Proteins / metabolism Gene Expression Regulation, Developmental Glycoproteins / metabolism Golgi Apparatus / metabolism Immunohistochemistry In Situ Hybridization Matrilin Proteins Mice Mice, Knockout Protein Transport Ribs / cytology Vesicular Transport Proteins / biosynthesis Vesicular Transport Proteins / genetics* Vesicular Transport Proteins / metabolism* |
| IF | 20.042 |
| Times Cited | 131 |
| WOS Category | CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | ATDC5(RCB0565) |