Title |
The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter
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Published in |
Human Molecular Genetics, April 2013
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DOI | 10.1093/hmg/ddt175 |
Pubmed ID | |
Authors |
Jeannette Abplanalp, Endre Laczko, Nancy J. Philp, John Neidhardt, Jurian Zuercher, Philipp Braun, Daniel F. Schorderet, Francis L. Munier, François Verrey, Wolfgang Berger, Simone M.R. Camargo, Barbara Kloeckener-Gruissem |
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. |
X Demographics
Geographical breakdown
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Australia | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 71 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 14 | 20% |
Student > Bachelor | 10 | 14% |
Researcher | 10 | 14% |
Student > Master | 6 | 8% |
Student > Doctoral Student | 5 | 7% |
Other | 10 | 14% |
Unknown | 16 | 23% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 16 | 23% |
Agricultural and Biological Sciences | 12 | 17% |
Pharmacology, Toxicology and Pharmaceutical Science | 10 | 14% |
Medicine and Dentistry | 9 | 13% |
Neuroscience | 2 | 3% |
Other | 6 | 8% |
Unknown | 16 | 23% |