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PERK-mediated translational control is required for collagen secretion in chondrocytes.
Hisanaga, Satoshi; Miyake, Masato; Taniuchi, Shusuke; Oyadomari, Miho; Morimoto, Masatoshi; Sato, Ryosuke; Hirose, Jun; Mizuta, Hiroshi; Oyadomari, Seiichi.
Affiliation
  • Hisanaga S; Division of Molecular Biology, Institute for Genome Research, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, 770-8503, Japan.
  • Miyake M; Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
  • Taniuchi S; Division of Molecular Biology, Institute for Genome Research, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, 770-8503, Japan.
  • Oyadomari M; Department of Molecular Research, Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, 770-8503, Japan.
  • Morimoto M; Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, 770-8503, Japan.
  • Sato R; Division of Molecular Biology, Institute for Genome Research, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, 770-8503, Japan.
  • Hirose J; Department of Molecular Research, Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, 770-8503, Japan.
  • Mizuta H; Division of Molecular Biology, Institute for Genome Research, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, 770-8503, Japan.
  • Oyadomari S; Department of Molecular Research, Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, 770-8503, Japan.
Sci Rep ; 8(1): 773, 2018 01 15.
Article de En | MEDLINE | ID: mdl-29335505
ABSTRACT
As chondrocytes are highly secretory and they experience a variety of stresses, physiological unfolded protein response (UPR) signalling is essential for extracellular matrix (ECM) secretion and chondrogenesis. In the three branches of the UPR pathway, PERK governs the translational attenuation and transcriptional upregulation of amino acid and redox metabolism and induction of apoptosis. It was previously demonstrated that a defect of the PERK branch of the UPR signalling pathway causes the accumulation of unfolded proteins, leading to cell death without perturbing endoplasmic reticulum (ER)-to-Golgi transport in pancreatic ß cells. However, little is known about the role of PERK in chondrocytes. In this study, we found that PERK signalling is activated in chondrocytes, and inhibition of PERK reduces collagen secretion despite causing excessive collagen synthesis in the ER. Perk -/- mice displayed reduced collagen in articular cartilage but no differences in chondrocyte proliferation or apoptosis compared to the findings in wild-type mice. PERK inhibition increases misfolded protein levels in the ER, which largely hinder ER-to-Golgi transport. These results suggest that the translational control mediated by PERK is a critical determinant of ECM secretion in chondrocytes.
Sujet(s)

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Collagène / Chondrocytes / EIF-2 Kinase Limites: Animals Langue: En Journal: Sci Rep Année: 2018 Type de document: Article Pays d'affiliation: Japon

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Collagène / Chondrocytes / EIF-2 Kinase Limites: Animals Langue: En Journal: Sci Rep Année: 2018 Type de document: Article Pays d'affiliation: Japon