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

Abstract

Creatine transport has been assigned to creatine transporter 1 (CRT1), encoded by mental retardation associatedSLC6A8. Here,weidentifieda secondcreatine transporter (CRT2)knownasmonocarboxylate transporter 12 (MCT12), encoded by the cataract and glucosuria associated gene SLC16A12. A non-synonymous alteration inMCT12 (p.G407S) found in a patientwith 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 preventivepower of creatine supplementation against the most prominent age-related vision impaired condition. © The Author 2013. Published by Oxford University Press. All rights reserved.