The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter.

Détails

ID Serval
serval:BIB_47C261C4BCFE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter.
Périodique
Human Molecular Genetics
Auteur(s)
Abplanalp J., Laczko E., Philp N.J., Neidhardt J., Zuercher J., Braun P., Schorderet D.F., Munier F.L., Verrey F., Berger W., Camargo S.M., Kloeckener-Gruissem B.
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
22
Numéro
16
Pages
3218-3226
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
Creatine transport has been assigned to creatine transporter 1 (CRT1), encoded by mental retardation associated SLC6A8. Here, we identified a second creatine transporter (CRT2) known as monocarboxylate transporter 12 (MCT12), encoded by the cataract and glucosuria associated gene SLC16A12. A non-synonymous alteration in MCT12 (p.G407S) found in a patient with age-related cataract (ARC) leads to a significant reduction of creatine transport. Furthermore, Slc16a12 knockout (KO) rats have elevated creatine levels in urine. Transport activity and expression characteristics of the two creatine transporters are distinct. CRT2 (MCT12)-mediated uptake of creatine was not sensitive to sodium and chloride ions or creatine biosynthesis precursors, breakdown product creatinine or creatine phosphate. Increasing pH correlated with increased creatine uptake. Michaelis-Menten kinetics yielded a Vmax of 838.8 pmol/h/oocyte and a Km of 567.4 µm. Relative expression in various human tissues supports the distinct mutation-associated phenotypes of the two transporters. SLC6A8 was predominantly found in brain, heart and muscle, while SLC16A12 was more abundant in kidney and retina. In the lens, the two transcripts were found at comparable levels. We discuss the distinct, but possibly synergistic functions of the two creatine transporters. Our findings infer potential preventive power of creatine supplementation against the most prominent age-related vision impaired condition.
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/08/2013 17:21
Dernière modification de la notice
08/05/2019 18:01
Données d'usage