When nicotine binds to a neuron, how does the cell know to send the signal that announces a smokers high"

As with other questions involving good sensations, the answer appears to be sugar.

A University of Southern California study appearing with a commentary in Nature Neuroscience online proposes a role for sugar as the hinge that opens a gate in the cell membrane and brings news of nicotines arrival.

Structural biologist Raymond Stevens of The Scripps Research Institute, who was not involved in the study, called it a landmark accomplishment for the fields of structural biology and neuronal cell signaling.

Besides substance addiction, Stevens pointed to epilepsy, schizophrenia and depression as targets for improved drugs that could result from the studys findings.

The study provides the first detailed look at part of the mouse nicotinic acetylcholine receptor (nAChR), one in a large and important group of molecules, known as ion channel proteins, that allow signals to pass between neurons.

The results reveal an important role for the sugar molecules in such proteins.

Our studies fill a major gap in the field and set a new paradigm, said Lin Chen, associate professor of molecular and computational biology at USC.

Many existing theories, which do not consider sugars role, are probably incomplete, Chen said.

The debate over how signals pass from the outside of a cell to the inside is a long-standing one.

Some researchers had suggested that when a chemical such as nicotine binds to an ion channel protein on the cell surface, the protein starts a conformational wave that propagates a signal through the protein body to the cell membrane, Chen said.

But the molecular basis of such a wave in nAChR or any other protein has not been clearly established.

Instead, the Chen groups study of crystal structure suggested a simple mechanical role for sugar mo
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Contact: Carl Marziali
marziali@usc.edu
213-740-4751
University of Southern California
22-Jul-2007