Gαo2Regulates Vesicular Glutamate Transporter Activity by Changing Its Chloride Dependence (original) (raw)

Abstract

Classical neurotransmitters, including monoamines, acetylcholine, glutamate, GABA, and glycine, are loaded into synaptic vesicles by means of specific transporters. Vesicular monoamine transporters are under negative regulation by α subunits of trimeric G-proteins, including Gαo2and Gαq. Furthermore, glutamate uptake, mediated by vesicular glutamate transporters (VGLUTs), is decreased by the nonhydrolysable GTP-analog guanylylimidodiphosphate. Using mutant mice lacking various Gα subunits, including Gαo1, Gαo2, Gαq, and Gα11, and a Gαo2-specific monoclonal antibody, we now show that VGLUTs are exclusively regulated by Gαo2. G-protein activation does not affect the electrochemical proton gradient serving as driving force for neurotransmitter uptake; rather, Gαo2exerts its action by specifically affecting the chloride dependence of VGLUTs. All VGLUTs show maximal activity at ∼5 mmchloride. Activated Gαo2shifts this maximum to lower chloride concentrations. In contrast, glutamate uptak...

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