Diff’rent Vesicles

A new discovery shows that the rules of synaptic transmission are very different from what we’d thought.

A synapse, blissfully unaware of the VAMP7s lurking in its midst.

In each neuron, tiny sacs called vesicles store neurotransmitter chemicals, and help transport them to other neurons. For decades, scientists had thought all the vesicles of a particular neurotransmitter were more or less identical – but now, they’ve discovered that only one set of vesicles are marked for transmission, while a much larger set lay mysteriously dormant.

What causes these differences, you ask? A protein with an awesome name:

We now find that the v-SNARE tetanus toxin-insensitive vesicle-associated membrane protein (VAMP7) differs from other synaptic vesicle proteins in its distribution to the two pools, providing evidence that they differ in molecular composition. We also find that both resting and recycling pools undergo spontaneous release, and when activated by deletion of the longin domain, VAMP7 influences the properties of release.

In other words, the presence of VAMP7 in a vesicle is an indicator of whether it’ll be released or not. This overturns the previous assumption that some vesicles get transmitted because – more or less – they’re in the right place at the right time. But now we know that vesicles don’t just get “discovered” like aspiring actresses – each one is born for its job, just as some of us are born to ride, run, or be wild.

As a paper published in the journal Neuron reports, a team led by UCSF’s Robert Edwards tagged various proteins with glowing (bioluminescent) molecules found in jellyfish. They found that VAMP7 levels are high in the resting pool of vesicles – the one that stays inside the neuron – but much lower in the recycling pool, which contains the vesicles that get transmitted, then recycled for later use.

Since the resting pool of vesicles can be 80 percent larger than the recycling pool, Edwards is sure it plays a significant purpose – but no one has any idea what that purpose is yet:

Resting vesicles are involved in a separate not-well-understood process in which neurons spontaneously release vesicles, which may help them adjust the types of connections they make with each other as well as the strength of those connections.

Since these vesicle differences may apply to all neurotransmitters in all neurons, it looks like we’ll need to correct some major misunderstandings about how the nervous system works. For one thing, we’ll probably need to reassess how we understand brain diseases whose symptoms stem from synaptic transmission problems.

It’s going to be really interesting to see what future research tells us about these resting vesicles, and what kinds of secret missions they get sent on when they’re not resting.

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