The SLC45-family of alternative sugar transporters in animals

• Applicants: Dr. Olga Vitavska; Professor Dr. Helmut Wieczorek
• Subject Area: Animal Physiology and Biochemistry
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 245044282

According to a classical tenet, transport of sugars across animal plasma membranes is performed by only two families of transporters. Secondary active transport occurs via Na+ symporters of the SLC5 gene family, while passive transport occurs via facilitative transporters of the SLC2 gene family. In recent years a new small protein family appeared in the vertebrate scenery which was called the SLC45 family of putative sugar transporters due to their apparent amino acid sequence similarity to plant sucrose transporters. One member of the mammalian SLC45 family, A1, was shown to be an H+/glucose symporter, while the properties of the other three members (A2-A4) were not known. Recently we investigated the orthologous Drosophila protein, Slc45-1, and characterized it as an H+/sucrose symporter. In not yet published observations we could show that the three mammalian proteins A2, A3 and A4 indeed transport sucrose in symport with H+. Further transported sugars are glucose, fructose and mannose. The H+-coupled transport of a disaccharide and the exceptional substrate specificity prompted us to name the SLC45 proteins the family of alternative sugar transporters.In this project we want, on the one hand, to continue our investigation of the Drosophila Slc45-1 protein in order to test our hypothesis that sugars including sucrose may play an important role as an absorbed nutrient as well as a compatible osmolyte. On the other hand, we want to analyze the murine SLC45 family members A2, A3 and A4. The identification of sucrose as a transported substrate challenges the long standing paradigm in Physiology that sugars are transported across membranes solely as monosaccharides. In addition, our detection of symport with H+ will provide novel important insights into the mechanisms of sugar transport in animals because it was so far believed generally to be Na+ dependent.

• DFG Programme: Research Grants