A new mechanism of dominance in hypophosphatasia: the mutated protein can disturb the cell localization of the wild-type protein |
| |
| Authors: | A. S. Lia-Baldini I. Brun-Heath C. Carrion B. Simon-Bouy J. L. Serre M. E. Nunes E. Mornet |
| |
| Affiliation: | (1) EA 4021, Biomolécules et thérapies antitumorales, CHU de Limoges, Limoges, France;(2) EA 2493, Université de Versailles - Saint Quentin en Yvelines, Versailles, France;(3) IFR 145, Confocal microscopy facility, Limoges, France;(4) Centre d’Etudes de Biologie Prénatale, SESEP, Centre hospitalier de Versailles, Le Chesnay, France;(5) Department of Pediatrics, The Ohio State University, Columbus, USA;(6) Laboratoire de biologie médicale, CHI Poissy - Saint Germain en laye, 10 rue du Champ Gaillard, BP 3082, 78303 Poissy, France |
| |
| Abstract: | 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. A. S. Lia-Baldini and I. Brun-Heath equally contributed to this work. |
| |
| Keywords: | |
| 本文献已被 PubMed SpringerLink 等数据库收录！ |
|
