Rat wild-type parathyroid hormone receptor (PTH-R) and mutant PTH-RP132L show the different intracellular localization in vitro

• SHIMOMURA-KUROKI Junko

  Pediatric Dentistry, The Nippon Dental University, School of Life Dentistry at Niigata

• UBAIDUS Sobhan

  Center for Transdisciplinary Research, Niigata University

• HL FREITAS Paulo

  Center for Transdisciplinary Research, Niigata University

• LI Minqi

  Center for Transdisciplinary Research, Niigata University

• ISHIDA Yoko

  Division of Biochemistry, Department of Tissue Regeneration and Reconstruction, Niigata University Faculty of Dentistry

• SAITO Naoaki

  Center for Transdisciplinary Research, Niigata University

• ODA Kimimitsu

  Center for Transdisciplinary Research, Niigata University Division of Biochemistry, Department of Tissue Regeneration and Reconstruction, Niigata University Faculty of Dentistry

• SHIMOOKA Shohachi

  Pediatric Dentistry, The Nippon Dental University, School of Life Dentistry at Niigata

• AMIZUKA Norio

  Center for Transdisciplinary Research, Niigata University

抄録

A replacement of proline with leucine at position 132 of the receptor for parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP), i.e., PTH-R, has been discovered in human Blomstrand's lethal chondrodysplasia. As skeletal deformities in this type of chondrodysplasia appear to compromise the receptor binding to its ligands, we examined the possibility that rat PTH-R carrying P132L mutation (PTH-R^P132L) would result in abnormal intracellular localization. Osteoblastic MC3T3-E1 cells were transfected with expression vectors containing cDNAs encoding either wild-type PTH-R or mutant PTH-R^P132L. The cells expressing the wild-type PTH-R produced a receptor protein with a molecular mass of 66.3 kDa, which localized its immunoreactivity mainly on the cell surfaces. In contrast, the PTH-R^P132L was hardly detected on the cell surfaces, but accumulated within the rough-surfaced endoplasmic reticulum. Consistent with this localization, the cells expressing the mutant receptor failed to generate cyclic AMP in response to PTH. Furthermore, a remarkably weaker intensity of the 66.3 kDa band compared with the wild-type counterpart suggests that PTH-R^P132L is prone to degradation in the transfected cells. In summary, these findings indicate that defective transport of PTH-R^P132L to the cell surface would be a molecular basis for Blomstrand's chondrodysplasia.

収録刊行物

• Biomedical Research

  Biomedical Research 29 (2), 61-69, 2008

  バイオメディカルリサーチプレス

キーワード

• General Biochemistry, Genetics and Molecular Biology
• General Medicine

詳細情報

• CRID: 1390001204900065920
• NII論文ID: 130004724050
• NII論文ID: 80019531498
• DOI: 10.2220/biomedres.29.61
• ISSN: 1880313X
• ISSN: 03886107
• Web Site: https://search.jamas.or.jp/link/ui/2008264793
• 本文言語コード: en
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