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Multiple functions of the first EGF domain in matrilin-3: Secretion and endoplasmic reticulum stress.
Wang, Yi-Chun; Liu, Jing-Shi; Chen, Jun-Yi; Wu, Sheng-Qi; Wang, Gui-Rong; Nie, Jing; Zhang, Shu-Kun; Guo, Qu-Lian; Luo, Jun-Ming.
Afiliação
  • Wang YC; Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
  • Liu JS; Department of Critical Care Medicine, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China.
  • Chen JY; Department of Critical Care Medicine, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China.
  • Wu SQ; Central Laboratory, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China.
  • Wang GR; Department of Surgery, SUNY Upstate Medical University College of Medicine, Syracuse, NY 13210, USA.
  • Nie J; Department of Critical Care Medicine, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China.
  • Zhang SK; Department of Pathology, Qinghai People's Provincial Hospital, Xining, Qinghai 810007, P.R. China.
  • Guo QL; Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
  • Luo JM; Department of Pathology, Qinghai People's Provincial Hospital, Xining, Qinghai 810007, P.R. China.
Int J Mol Med ; 36(6): 1648-56, 2015 Dec.
Article em En | MEDLINE | ID: mdl-26499313
Mutations in matrilin-3 are associated with common skeletal diseases, such as hand osteoarthritis (HOA), as well as rare chondrodysplasias, such as multiple epiphyseal dysplasia (MED) and spondyloepimetaphyseal dysplasia (SEMD). In the present study, we constructed the mutations R116W [at the von Willebrand factor, type A (vWFA) domain], T298M [at the first epidermal growth factor (EGF) domain] and C299S (at the first EGF domain), according to the mouse sequence, which are associated with human MED, HOA and SEMD, respectively, by overlap extension PCR and inserted them into an expression vector (pcDNA3.1/v5-His). We transfected these contructs into the COS-1 or MCT cells, and the results revealed that the HOA-related matrilin-3 mutation (T298M) leads to a high expression level of growth arrest DNA damage-inducible gene 153 (GADD153, also known as CHOP; an endoplasmic reticulum stress marker), as shown by western blot analysis and does not significantly affect protein secretion, as shown by immunofluorescence staining; however, osteochondroplasia, i.e., MED-related (R116W) and SEMD-related (C299S) mutations lead to both high levels of GADD153 expression and protein trafficking into the cytoplasm and form multiple vacuoles in cells, which in turn leads to insufficient protein secretion.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Mutantes / Estresse do Retículo Endoplasmático / Proteínas Matrilinas / Mutação Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Mutantes / Estresse do Retículo Endoplasmático / Proteínas Matrilinas / Mutação Idioma: En Ano de publicação: 2015 Tipo de documento: Article