Fig. 3.

Model of transport and ion binding of VGLUTs. One model that has been proposed to describe the uptake of glutamate by VGLUTs is based on the alternate access model [177]. a VGLUTs have several binding sites for transported ions: glutamate, Cl⁻, K⁺ and H⁺ (and Na⁺ and Pi). b In high chloride concentrations and in the cytosol upon open conformation, VGLUT is loaded with one glutamate, one Cl⁻, and partially by one K⁺. Glutamate and K⁺ are released into the lumen when VGLUT shifts to a lumen open conformation (step 1). At this stage, the anionic binding site is filled with another Cl⁻ while the cationic site loads one proton (step 2). Finally, VGLUT reopens in the cytosol where it releases one Cl⁻ and one proton (step 3). c In the presence of low luminal concentrations of chloride, VGLUT follows the same steps as in b but during step 2, the partially filled cationic site is fully occupied by a proton, while only a few chloride ions are released into the cytosol in step 3