Vesicular inhibitory amino acid transporter

Vesicular inhibitory amino acid transporter (VIAAT), also known as vesicular GABA transporter (VGAT), is a protein that in humans is encoded by the SLC32A1 gene. VIAAT/VGAT is essential for the uptake of the inhibitory neurotransmitters gamma-aminobutyric acid (GABA) and glycine into synaptic vesicles, facilitating their storage and subsequent release into the synapse. This process is crucial for the regulation of neurotransmission in the central nervous system (CNS), affecting various physiological and psychological processes.

Function

VIAAT/VGAT plays a pivotal role in inhibitory neurotransmission by packaging GABA and glycine into synaptic vesicles within the nerve terminal. This action prepares these neurotransmitters for release into the synaptic cleft, where they can bind to their respective receptors on post-synaptic neurons. The binding of GABA or glycine to their receptors typically results in the hyperpolarization of the neuron, making it less likely to fire an action potential. This mechanism is fundamental in maintaining the balance between excitation and inhibition within the CNS, crucial for normal brain function and preventing excessive neuronal activity that could lead to disorders such as epilepsy.

Structure

The VIAAT/VGAT protein is a member of the solute carrier family (SLC), specifically the SLC32 subfamily. It is an integral membrane protein that spans the membrane of synaptic vesicles. The structure of VIAAT/VGAT includes transmembrane domains that facilitate the transport of GABA and glycine into vesicles, utilizing a proton gradient as the driving force for neurotransmitter uptake.

Clinical Significance

Alterations in the expression or function of VIAAT/VGAT can have significant implications for neurological health. Dysregulation of inhibitory neurotransmission, potentially due to issues with VIAAT/VGAT, has been implicated in a variety of neurological and psychiatric disorders, including epilepsy, anxiety disorders, and schizophrenia. Understanding the role and mechanisms of VIAAT/VGAT in neurotransmission can contribute to the development of therapeutic strategies for these conditions.

Research

Research on VIAAT/VGAT has focused on elucidating its role in neurotransmitter transport, its structure-function relationships, and its involvement in neurological disorders. Studies using animal models, particularly genetically modified mice lacking VIAAT/VGAT, have provided valuable insights into the essential role of inhibitory neurotransmission in brain function and behavior.