VMAT2

Overview

The Vesicular Monoamine Transporter 2 (VMAT2) is a protein that in humans is encoded by the SLC18A2 gene. VMAT2 is an integral membrane protein that transports monoamines—such as dopamine, norepinephrine, serotonin, and histamine—from the cytosol into synaptic vesicles. This process is crucial for the storage and subsequent release of these neurotransmitters into the synaptic cleft, where they can exert their effects on post-synaptic receptors.

Structure

VMAT2 is a member of the solute carrier family 18 (SLC18), which is characterized by its ability to transport monoamines across cellular membranes. The protein is composed of 12 transmembrane domains, which form a channel through which monoamines are translocated. The transport process is driven by a proton gradient across the vesicular membrane, which is maintained by a vesicular H+-ATPase.

Function

The primary function of VMAT2 is to sequester monoamines into synaptic vesicles, thereby regulating their availability for release during neurotransmission. By controlling the storage and release of monoamines, VMAT2 plays a critical role in modulating mood, arousal, and various cognitive functions. Dysregulation of VMAT2 activity has been implicated in several neurological and psychiatric disorders, including Parkinson's disease, depression, and schizophrenia.

Clinical Significance

VMAT2 is a target for several pharmacological agents. For instance, the drug reserpine inhibits VMAT2, leading to the depletion of monoamines from synaptic vesicles and a reduction in neurotransmitter release. This mechanism underlies the antihypertensive and antipsychotic effects of reserpine. Conversely, drugs that enhance VMAT2 activity, such as amphetamines, increase the release of monoamines and are associated with stimulant effects.

Research and Applications

Research on VMAT2 has expanded our understanding of its role in various diseases. Imaging studies using VMAT2 ligands, such as PET scans with radiolabeled tracers, have been employed to assess dopaminergic function in the brain. These studies are particularly useful in the diagnosis and monitoring of Parkinson's disease and other movement disorders.

Also see

• Monoamine neurotransmitter
• Dopamine
• Serotonin
• Parkinson's disease
• Neurotransmitter transporters

External links

• SLC18A2 gene - NCBI
• VMAT2 - UniProt