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

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Ressource 1Download: serval:BIB_47C261C4BCFE.P001 (325.03 [Ko])
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Serval ID
serval:BIB_47C261C4BCFE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter.
Journal
Human Molecular Genetics
Author(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
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
22
Number
16
Pages
3218-3226
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
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
Yes
Create date
22/08/2013 17:21
Last modification date
25/09/2019 7:09
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