Glucose transport families SLC5 and SLC50.

There are three families of glucose transporters in the human genome, SLC2, SLC5 and SLC50. Here I review the structure and function of the SLC5 and SLC50 genes. The human sodium glucose cotransporter family (SLC5) has 12 human genes expressed in tissues ranging from epithelia to the central nervous system. The functions of all are known based on studies using heterologous expression systems: 10 are tightly coupled plasma membrane Na(+)/substrate cotransporters for solutes such as glucose, myoinositol, and anions; 1 is a Na(+)/Cl(-)/Choline cotransporter; and another is a glucose activated ion channel. The exon organization of most of the genes is similar in that they contain 14-15 exons. However, the choline transporter CHT is encoded in by the 8 exon SLC5A7 gene and the myoinositol SMIT transporter by the 1 exon SLC5A3 gene. Mutations in 3 SLC5 genes produce genetic phenotypes (glucose-galactose-malabsorption, renal glucosuria and hypothyroidism). Members of the SLC5 family are multifunctional membrane proteins in that they also behave as uniporters, urea and water channels, and urea and water cotransporters. The atomic structure of a closely related bacterial homolog has been solved and the structural core is common to six unrelated transporters, e.g. members of the SLC6 family of neurotransporters, and this leads to the conclusion that these work by a similar mechanism. The new SWEET class of glucose uniporters, SLC50, only has only one member in the human genome, SLC50A1. The SWEETs are found mostly in plants where they appear to be responsible for sugar efflux and are targeted by pathogens and symbionts for nutrition.