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Hum Mol Genet
2013 Aug 15;2216:3218-26. doi: 10.1093/hmg/ddt175.
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The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter.
Abplanalp J
,
Laczko E
,
Philp NJ
,
Neidhardt J
,
Zuercher J
,
Braun P
,
Schorderet DF
,
Munier FL
,
Verrey F
,
Berger W
,
Camargo SM
,
Kloeckener-Gruissem B
.
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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.
Immunofluorescence images. Membrane localization of human MCT12 (hMCT12) in Xenopus laevis oocytes injected with SLC16A12 cRNA. Noninjected oocytes and those injected with the chaperone CD147 alone served as controls (top row). Membrane localized signals (arrow) were detected only in oocytes injected with MCT12, irrespective of the presence of chaperone CD147.
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