Proton-associated sucrose transport of mammalian Solute Carrier Family 45: an analysis in Saccharomyces cerevisiae

The members of the solute carrier family 45 (SLC45) have been implicated with the regulation of glucose homeostasis in the brain (SLC45A1), with skin and hair pigmentation (SLC45A2), and with prostate cancer and myelination (SLC45A3). However, apart from A1, a proton-associated glucose transporter, the function of these proteins is still largely unknown although sequence similarities to plant sucrose transporters mark them as a putative sucrose transporter family. Heterologous expression of the three members SLC45A2, SLC45A3 and SLC45A4 in Saccharomyces cerevisiae confirmed that they are indeed sucrose transporters. 14C-sucrose uptake measurements revealed intermediate transport affinities with Km values around 5 mM. Transport activities were best under slightly acidic conditions and were inhibited by the protonophore CCCP, demonstrating an H+-coupled transport mechanism. Na+, on the other hand, had no effect on sucrose transport. Competitive inhibition assays indicated a possible transport also of glucose and fructose. Real time PCR of mouse tissues confirmed mRNA expression of SLC45A2 in eyes and skin and of SLC45A3 primarily in the prostate, but also in other tissues, whereas SLC45A4 showed predominantly a ubiquitous expression. Altogether the results provide new insights into the physiological significance of SLC45 family members and challenge existing concepts of mammalian sugar transport, as they i) transport a disaccharide and ii) perform secondary active...
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research