Nobel Prize winner reports new model for neurotransmitter release

October 10, 2013
This is a molecular model of the active zone protein complex and its relation to the synaptic vesicle fusion machinery, Ca2+ channels, and synaptic cell-adhesion molecules. Credit: Neuron, Volume 75, Issue 1, 11-25, 12 July 2012, Sudhof

In a Neuron article published online October 10th, recent Nobel Laureate Thomas C. Südhof challenges long-standing ideas on how neurotransmitter gets released at neuronal synapses. On October 7th, Südhof won the Nobel Prize in Physiology or Medicine, alongside James Rothman and Randy Schekman, for related work on how vesicles—such as those in neurons that contain neurotransmitter—are transported within cells.

Neurotransmitter-containing vesicles are found inside very close to the end of the axon. Here, they can quickly fuse with the neuronal membrane surrounding the axon to spill their contents into the synapse. How these vesicles are able to fuse with the membrane has been controversial, however, and understanding this process would give researchers much greater insight how neurons communicate with each other. Previously, it was thought that proteins found on the outside of the vesicles and on the axon membrane (called SNARE proteins) would come together and physically form a pore through which the contents of the vesicle—the —could be released into the synapse. Now, the new findings from Südhof suggest that these proteins may not form a pore at all. Instead, their main role may be to physically force the vesicle and the axon membrane to get very close to each other; once they are forced into contact, the two appear able to fuse spontaneously.

"The importance of SNARE transmembrane regions has never been tested in a physiological fusion reaction," says Dr. Südhof. "We show that the SNARE transmembrane regions are dispensible for fusion as such but are important for maintaining the normal efficiency of regulated fusion. These findings rule out an essential participation of the SNARE transmembrane regions in fusion and are consistent with the notion that the SNAREs function in fusion as force generators, i.e., that their function is to force the membranes close together." The results are controversial due to years of research supporting the SNARE-protein pore hypothesis. These provocative findings could change long-held models for how neurotransmitters are released from neurons and suggest that there remain many open questions about the role of SNAREs in neurotransmitter release at synapses.

Explore further: Study uses Botox to find new wrinkle in brain communication

More information: Neuron, Zhou et al.: "Lipid-Anchored SNAREs Lacking Transmembrane Regions Fully Support Membrane Fusion during Neurotransmitter Release."

Related Stories

Study uses Botox to find new wrinkle in brain communication

May 2, 2013

National Institutes of Health researchers used the popular anti-wrinkle agent Botox to discover a new and important role for a group of molecules that nerve cells use to quickly send messages. This novel role for the molecules, ...

What happens when synapses run out of transmitter?

October 9, 2013

(Medical Xpress)—The recent Nobel Prize Award in Medicine highlights the importance of vesicle-based transport for different kinds of cells. One of the recipients, Thomas Sudhof, has contributed extensively to our current ...

Recommended for you

Closing the loop with optogenetics

August 28, 2015

An engineering example of closed-loop control is a simple thermostat used to maintain a steady temperature in the home. Without it, heating or air conditioning would run without reacting to changes in outside conditions, ...

Self-control saps memory, study says

August 26, 2015

You're driving on a busy road and you intend to switch lanes when you suddenly realize that there's a car in your blind spot. You have to put a stop to your lane change—and quickly.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.