A new mechanism of dominance in hypophosphatasia: the mutated protein can disturb the cell localization of the wild-type protein - Université de Limoges Accéder directement au contenu
Article Dans Une Revue Human Genetics Année : 2008

A new mechanism of dominance in hypophosphatasia: the mutated protein can disturb the cell localization of the wild-type protein

I. Brun-Heath
  • Fonction : Auteur
B. Simon-Bouy
  • Fonction : Auteur
J. L. Serre
  • Fonction : Auteur
M. E. Nunes
  • Fonction : Auteur
E. Mornet
  • Fonction : Auteur

Résumé

The dominant negative effect of mutations is rare in metabolic diseases and its mechanism has not been studied much. Hypophosphatasia, a bone inherited metabolic disorder, is a good model because the disease can be dominantly transmitted. The gene product activity depends on a homodimeric configuration and many mutations have been reported in the ALPL gene responsible for the disease. Using CFP/YFP-tagged-TNSALP plasmids, transfections in COS cells and confocal fluorescence analyses, we studied the point mutation G232V (c.746G>T). We showed that the G232V protein sequestrates some of the wild-type protein into the cells and prevents it from reaching the membrane where it plays its physiological role.

Dates et versions

hal-00651340 , version 1 (13-12-2011)

Identifiants

Citer

Anne-Sophie Lia-Baldini, I. Brun-Heath, Claire Carrion, B. Simon-Bouy, J. L. Serre, et al.. A new mechanism of dominance in hypophosphatasia: the mutated protein can disturb the cell localization of the wild-type protein. Human Genetics, 2008, 123 (4), pp.429-32. ⟨10.1007/s00439-008-0480-1⟩. ⟨hal-00651340⟩
45 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More