Mammalian Sugar Transporter Families: GLUT and SGLT

Abstract

Sugar transport across the plasma membrane of mammalian cells is mediated by members of the GLUT/SLC2A family of facilitative sugar transporters (Joost and Thorens 2001; Mueckler 1994; Seatter and Gould 1999; Uldry and Thorens 2004) and the SGLT/SLC5A family of Na+-dependent sugar transporters (Wood and Trayhurn 2003). These proteins belong to a larger superfamily of proteins known as the major facilitator superfamily (MFS) or uniporter-symporter-anti-porter family (Saier et al. 1999a) The MFS family is one of the two largest families of membrane transporters in nature and accounts for nearly half of the solute transporters encoded within the genomes of microorganisms (bacteria, yeasts) and higher organisms such as plants and animals. The MFS was originally thought to function primarily in the uptake of sugars, but more detailed studies of members of this family have revealed that drug efflux systems, Krebs cycle metabolites, organophosphate: phosphate exchangers, oligosaccharide: H1 symport permeases, and bacterial aromatic acid permeases are also members of the MFS superfamily. These observations led to the probability that the MFS is far more widespread in nature and far more diverse in function than had been thought previously (Pao et al. 1998; Saier et al. 1999a, 1999b, 1998). Thus far 17 subgroups of the MFS have been identified. The human genome project has identified 14 members of the GLUT/SLC2A family which have been cloned in humans (Wood and Trayhurn 2003; Wu and Freeze 2002) (Fig. 6, Table 1). GLUT proteins are characterized by the presence of 12 membrane spanning helices and several conserved sequence motifs (Joost and Thorens 2001). The GLUT/SLC2A proteins are expressed in a tissue- and cell-specific manner and exhibit distinct kinetic and regulatory properties that reflect their functional and tissue-specific roles. The full definitions and unique functional characteristics for each of the GLUT protein isoforms are outlined in Table 1. The sequence similarities of the GLUT/SLC2A family members are now well defined and the family is now divided into three subclasses (Fig. 6). Five of the mammalian facilitated glucose carriers (GLUTs 1-5) have been very well characterized, but significantly less is known about the remaining nine glucose carriers (GLUTs 6-14) since their discovery in late 2001 (Joost and Thorens 2001) and much remains to be learned about their expression, tissue distribution, and transport functions (Uldry and Thorens 2004). Of these 14 glucose transporter genes, nine are known to be expressed at the mRNA level in chondrocytes (Richardson et al. 2003) (see subsequent sections). © 2008 Springer-Verlag Berlin Heidelberg.