Title : Identified new regulation of vesicular neurotransmitter transporters
Abstract:
Neurotransmitter is an essential for synaptic transmission in the mammalian central nervous system, and is involved in all brain functions and in various neurological diagnoses. Vesicular neurotransmitter transporters (VNTs) are one of major syanptic vesicle proteins. They transport neurotransmitter into synaptic vesicles for excitatory, inhibitory or emotional signal transmission in the central nervous system. VNTs are located not only on synaptic vesicles, but also on the plasma membrane during the transduction of neurons. VNTs are also involved in various biochemical regulation processes. I have clarified the some of molecular mechanisms of VNTs, I will talk about the lipid regulation of VNTs in this presentation.
Presynaptic terminals tightly control their lipid composition, and each lipid markedly regulates neuronal activity. The lipid compositions and protein orientations are different among synaptic vesicles and plasma membranes in presynaptic terminals and VNTs are localized on both membrane. Several physiological and pathological conditions induce changes in the lipid composition, and lipidomic changes are associated with neurological and psychiatric disorders.
In the present study, we demonstrate the lipid induced transporter activity and conformational changes. And this lipid regulation is linked to the transporter cycle during the neurotransmission. That is, VNTs actively accumulate neurotransmitters in synaptic vesicles, but upon exocytosis, they abruptly stop their transport and relase excess neurotransmitters. Because neurological and psychiatric disorders are also caused by abnormalities in vesicular neurotransmitter transporters, the lipidomic regulation of these transporters will serve as appropriate drug targets for these disorders. Thus, our findings could provide novel strategies for the treatment and prevention of neurological and psychiatric disorders.
