MAMMALIAN ION-COUPLED SOLUTE TRANSPORTERS

Active transport of solutes into and out of cells proceeds via special ized transporters that utilize diverse energy-coupling mechanisms. Ion -coupled transporters link uphill solute transport to downhill electro chemical ion gradients. In mammals, these transporters are coupled to the cotransport of H+, Na+, Cl- and/or to the countertransport of K+ o r OH-. By contrast, ATP-dependent transporters are directly energized by the hydrolysis of ATP. The development of expression cloning approa ches to select cDNA clones solely based on their capacity to induce tr ansport function in Xenopus oocytes has led to the cloning of several ion-coupled transporter cDNAs and revealed new insights into structura l designs, energy-coupling mechanisms and physiological relevance of t he transporter proteins. Different types of mammalian ion-coupled tran sporters are illustrated by discussing transporters isolated in our ow n laboratory such as the Na+/glucose co-transporters SGLT1 and SGLT2, the H+(-)coupled oligopeptide transporters PepT1. and PepT2, and the N a+- and K+-dependent neuronal and epithelial high affinity glutamate t ransporter EAAC1. Most mammalian ion-coupled organic solute transporte rs studied so far can be grouped into the following transporter famili es: (1) the predominantly Na+-coupled transporter family which include s the Na+/glucose cotransporters SGLT1, SGLT2, SGLT3 (SAAT-pSGLT2) and the inositol transporter SMIT, (2) the Na+-and Cl--coupled transporte r family which includes the neurotransmitter transporters of gamma-ami no-butyric acid (GABA), serotonin, dopamine, norepinephrine, glycine a nd proline as well as transporters of p-amino acids, (3) the Na+- and K+-dependent glutamate/neurotransmitter family which includes the high affinity glutamate transporters EAAC1, GLT-1, GLAST, EAAT4 and the ne utral amino acid transporters ASCT1 and SATT1, reminiscent of system A SC and (4) the H+-coupled oligopeptide transporter family which includ es the intestinal H+-dependent oligopeptide transporter PepT1.