Kiss and Run at the Synapse

Recycling program. Vessicles can be recycled three different ways after dumping their contents into the synapse.

The dizzying activity of a brain relies on neurons that chit-chat using chemical signals. Two new papers help clarify exactly how the cell releases these essential messengers.

When an electrical impulse travels to the end of a neuron, it triggers the release of chemicals into the gap, or synapse, between neurons. These neurotransmitters stimulate electrical activity in the neighboring neuron. Neurons store neurotransmitters in vesicles, which wait near the cell membrane for the message to dump their contents into the synapse. Thirty years ago, researchers showed that after releasing its cargo, a vesicle collapses and its membrane fuses with the cell membrane. Reconstructing the vesicle requires a complex series of steps and can take up to 30 seconds--an eternity in the time scale of neural communication. Researchers suspected that neurons had a quicker trick as well, which they dubbed "kiss-and-run": The vesicle opens briefly, releases the neurotransmitter, then snaps shut and remains ready to smooch again.

Now neurons have been caught in the act. Neuroscientists Charles Stevens and Sunil Gandhi of the Salk Institute in La Jolla, California, genetically attached a protein in the walls of synaptic vesicles to a pH-sensitive protein that glowed when the vesicle opened, exposing its acidic interior to the neutral environment outside. After some tinkering, the scientists glimpsed single vesicles, and by watching how long a vesicle glowed, they could determine how long it was open. In the 5 June issue of Nature, they report that vesicles release neurotransmitter three ways: the classical mode, in which the vesicle collapses and becomes part of the cell membrane before being reconstructed and reused; the "kiss-and-run" mode, in which the vesicle opens for just half a second and then closes; and an unexpected third mode in which the vesicle gets stuck in the cell membrane, where it remains trapped until the next electrical impulse frees it.

A second paper in the same issue reports a similar finding. Neuroscientist Richard Tsien at Stanford University and his colleagues filled vesicles with fluorescent dye and watched the dye escape when the vesicle opened. Most vesicles, they found, released only some of the dye, indicating that the vesicle may have closed before all the dye could get out, as would happen in the "kiss-and-run" scenario. Subsequent impulses spurred some vesicles to release more dye, indicating that a single vesicle can remain in place and be reused.

"There's a good chance [this research] is going to be in textbooks someday," says physiologist William Betz of the University of Colorado Medical School in Denver. Betz says that neurons in different parts of the brain likely use both the classical mode and the kiss-and-run mode depending on the requirements for fast turnover. "It's a joyous situation where everybody's correct."

Related Sites
Betz lab home page
Stevens lab home page
Tsien lab home page

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