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: Life in a bubble: Nobel secrets of body's cell transport system

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

Related Stories

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 ...

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, ...

Recommended for you

Knowing one's place in a social hierarchy

December 7, 2016

When you start a new job, it's normal to spend the first day working out who's who in the pecking order, information that will come in handy for making useful connections in the future. In an fMRI study published December ...

Deep brain stimulation may not boost memory

December 7, 2016

Deep brain stimulation (DBS) of areas in the brain known to be involved in making memories does not improve memory performance, according to a study by Columbia University researchers published December 7 in Neuron. The study ...

Brain activity may predict risk of falls in older people

December 7, 2016

Measuring the brain activity of healthy, older adults while they walk and talk at the same time may help predict their risk of falls later, according to a study published in the December 7, 2016, online issue of Neurology.

When neurons are 'born' impacts olfactory behavior in mice

December 7, 2016

New research from North Carolina State University shows that neurons generated at different life stages in mice can impact aspects of their olfactory sense and behavior. The work could have implications for our understanding ...

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.