Characterization of Novel Solute Carriers in Humans, Mice and Flies : Solute Carriers in a Broad and Narrow Perspective

Abstract: The solute carrier family is the largest family of membrane-bound transporters in humans, with 430 members divided into 65 subfamilies. They transport various substrates across lipid barriers and are vital for absorption, distribution, metabolism and excretion in all cell types in the body. Despite being involved in vital functions, and their effect on both physiology and pathophysiology, many transporters are not characterized. The aim of this thesis was to study newly identified putative solute carriers of which little is known. In Paper I, the relationship of solute carriers in humans and fruit flies was studied. The study revealed that 54 of the 65 subfamilies in humans have one or more orthologues in fruit flies, and a total of 381 orthologues were identified in fruit flies. In Paper II, a comprehensive study of the putative solute carriers and their response to different sugar concentrations were performed. Several, but not all, putative solute carriers were altered in cell cultures maintained in media containing low or no glucose, and the expression normalized upon refeeding with glucose. Similar results were observed in fruit flies subjected to complete starvation or diets with varying sugar concentrations. Last, in Paper III and IV, characterization of one putative solute carrier, UNC93A, was performed. The studies revealed that UNC93A was a conserved protein with an abundant expression in the body of mice but with a restricted expression in fruit flies. The protein was found to possibly be expressed at, or close to, the plasma membrane of cells and to co-localize with Twik-Acid sensitive potassium channels. UNC93A was found to be important for the renal function in fruit flies and to affect survival and membrane potentials in cells. The findings of this thesis establish a high conservation of several putative solute carriers and that they have a highly dynamic regulation during fluctuating energy and glucose availability. Further, while several clear biological aspects of UNC93A was identified, the exact function of transporter proteins is cumbersome to find and more research about these transporters is needed to fully understand their mechanistic role and their association and/or involvement in health and sickness.