Evolutionary ancestry and novel functions of the mammalian glucose transporter (GLUT) family
1 Department of Medicine-St. Vincent's, The University of Melbourne, Fitzroy, Victoria 3065, Australia
2 Department of Genetics, The University of Melbourne, Parkville, Victoria 3052, Australia
3 Department of Botany, The University of Melbourne, Parkville, Victoria 3052, Australia
4 Department of Primary Industries, Victorian Agribiosciences Centre, Bundoora, Victoria 3983, Australia
5 Protein Chemistry and Metabolism Unit, St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia
BMC Evolutionary Biology 2010, 10:152 doi:10.1186/1471-2148-10-152Published: 21 May 2010
In general, sugar porters function by proton-coupled symport or facilitative transport modes. Symporters, coupled to electrochemical energy, transport nutrients against a substrate gradient. Facilitative carriers transport sugars along a concentration gradient, thus transport is dependent upon extracellular nutrient levels. Across bacteria, fungi, unicellular non-vertebrates and plants, proton-coupled hexose symport is a crucial process supplying energy under conditions of nutrient flux. In mammals it has been assumed that evolution of whole body regulatory mechanisms would eliminate this need. To determine whether any isoforms bearing this function might be conserved in mammals, we investigated the relationship between the transporters of animals and the proton-coupled hexose symporters found in other species.
We took a comparative genomic approach and have performed the first comprehensive and statistically supported phylogenetic analysis of all mammalian glucose transporter (GLUT) isoforms. Our data reveals the mammalian GLUT proteins segregate into five distinct classes. This evolutionary ancestry gives insight to structure, function and transport mechanisms within the groups. Combined with biological assays, we present novel evidence that, in response to changing nutrient availability and environmental pH, proton-coupled, active glucose symport function is maintained in mammalian cells.
The analyses show the ancestry, evolutionary conservation and biological importance of the GLUT classes. These findings significantly extend our understanding of the evolution of mammalian glucose transport systems. They also reveal that mammals may have conserved an adaptive response to nutrient demand that would have important physiological implications to cell survival and growth.