Structural determinants of binding of the creatine transporter (creat, SLC6A8) inform the functional annotation of the SLC6 transporters family

The solute carrier 6 (SLC6) family of transporters comprises 20 members with great pharmacological impact, as they transport neurotransmitters, amino acids, betaine, taurine and creatine across the cells. Most of the time, transporters are studied individually or by subgroup. Notably, members of the monoamine subgroup—containing the norepinephrine transporter NET (SLC6A2), the dopamine transporter DAT (SLC6A3) and the serotonin transporter SERT (SLC6A4)—have been extensively studied. These findings provide precious insight into the three-dimensional architectures of these transporters, as well as their mechanism of transport and modulation.