Cotransporter

Cotransporters are membrane proteins that move two or more solutes across a cell membrane in a coupled process. They are a type of secondary active transporter, meaning they rely on the electrochemical gradient of one substrate, usually an ion such as Na+ or H+, to drive the transport of another substrate against its gradient. The energy stored in the gradient is the source that enables uphill transport of the second solute.

Cotransporters are classified as symporters or antiporters. In symporters, the transported substrates move in the same direction across the membrane. In antiporters, the substrates move in opposite directions. Both types couple the movement of the downhill ion to the uphill transport of the second solute, and neither requires direct ATP hydrolysis to function. Primary active transporters (for example, Na+/K+-ATPase) maintain the ion gradients that power cotransporters.

Common examples include the sodium-glucose cotransporters SGLT1 and SGLT2, which use Na+ influx to bring glucose into intestinal epithelial cells and renal proximal tubule cells, respectively. These transporters are targets for diabetes treatments with SGLT2 inhibitors. Another major family is the Na+/K+/2Cl− cotransporters (NKCC1 and NKCC2); NKCC2 in the thick ascending limb of the loop of Henle is inhibited by loop diuretics to promote diuresis. The Na+/Ca2+ exchanger (NCX) is an antiporter that exchanges Na+ for Ca2+ across the membrane in excitable tissues. Bacterial lactose permease LacY is a H+-coupled symporter that uses the proton motive force to import lactose.

Cotransporters play essential roles in nutrient uptake, electrolyte balance, pH regulation, and overall cellular homeostasis.