Scientists at St. Jude Uncover Neurotransmitter Transporter Structure, Offering New Insights in Neuropharmacology

by François Dupont
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St. Jude Children’s Research Hospital’s team has achieved a significant breakthrough in understanding VMAT2, a key neurotransmitter transporter. This development is pivotal in comprehending how it interacts with medications used for treating conditions like Tourette syndrome, thus contributing greatly to neuropharmacological research.

At the core of neuronal communication are neurotransmitters. The researchers at St. Jude, applying their advanced knowledge in structural biology, have successfully determined the structure of vesicular monoamine transporter 2 (VMAT2), essential for neuronal signaling.

This discovery, achieved by observing VMAT2 in various states, allows a deeper understanding of its functioning and the impact of its structural changes on drug interaction. This is a crucial step in developing treatments for hyperkinetic disorders, including Tourette syndrome. The findings were published in the journal Nature.

Understanding Neuronal Communication

Monoamines, such as dopamine, serotonin, and adrenaline, are central to neuronal communication, influencing brain functions like emotions, sleep, and movement. These neurotransmitters are produced and released by neurons and must be packaged into vesicles before release.

Vesicles, akin to cargo ships in the neuronal cell, store neurotransmitters to be released at synapses. VMATs, located on vesicle membranes, transport monoamines into these vesicles, functioning similarly to cranes on cargo ships.

Lead researchers Chia-Hsueh Lee, Ph.D., Shabareesh Pidathala, Ph.D., and Yaxin Dai, Ph.D., from St. Jude’s Department of Structural Biology, have provided significant insights into VMAT2’s role in neurotransmitter packaging.

Once VMAT2 loads the vesicles with monoamines, these vesicles travel to the synaptic gap to release their chemical contents.

Varieties and Importance of VMAT

There are two VMAT types: VMAT1, found in neuroendocrine cells, and VMAT2, widespread in the neuronal system and of significant clinical importance.

“VMAT2’s physiological role is

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