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

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

Abplanalp, Jeannette
•
Laczko, Endre
•
Philp, Nancy J.
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2013
Human Molecular Genetics

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. MichaelisMenten kinetics yielded a V-max of 838.8 pmol/h/oocyte and a K-m of 567.4 m. 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.

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Type
research article
DOI
10.1093/hmg/ddt175
Web of Science ID

WOS:000322341300004

Author(s)
Abplanalp, Jeannette
Laczko, Endre
Philp, Nancy J.
Neidhardt, John
Zuercher, Jurian
Braun, Philipp
Schorderet, Daniel F.
Munier, Francis L.
Verrey, Francois
Berger, Wolfgang
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Date Issued

2013

Publisher

Oxford University Press

Published in
Human Molecular Genetics
Volume

22

Issue

16

Start page

3218

End page

3226

Note

National Licences

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
SV  
Available on Infoscience
October 1, 2013
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/95619
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