Neurotransmitters and vesicles

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You know the names of some neurotransmitters: dopamine, serotonin, norepinephrine. Glutamate is the major excitatory neurotransmitter and GABA is the major inhibitory one, right?. All neurotransmitters function in a similar way to communicate between two neurons. The pre-synaptic neuron sends messages in the form of neurotransmitter for the post-synaptic neuron to receive at neurotransmitter receptors.

Let’s focus on the pre-synaptic side for a minute. Neurotransmitters aren’t released one at a time. They are released in bulk, thousands at once. This is achieved by packaging the neurotransmitters up into a little sac in the pre-synaptic termincal called a synaptic vesicle. You can see hundreds of these in electron micrographs of synapse.

When the pre-synaptic neuron gets the cue to dump neurotransmitters, the vesicle, which has a lipid bilayer membrane just like the cell’s membrane, fuses with the cell membrane through an elaborate protein winching mechanism. This releases the entire vesicle contents into the synapse at once. This process isn’t entirely understood, but many of the major proteins that interact between the cell membrane and the vesicle membrane are known. So a group recently did a ton of mass spec and quantitative measurements to determine more precisely the protein content of a given synaptic vesicle and produces a model vesicle. I think it is just lovely:


They found that a surpising amount of the membrane space on a vesicle was ‘dedicated’ meaning that it either contained a trans-membrane protein or certain lipid molecules that are unlikely to flow around very much within the membrane. Here is one of my favorite passages:

A picture is emerging in which the membrane resembles a cobblestone pavement, with the proteins organized in patches that are surrouneded by lipid rims, rather than icebergs floating in a sea of lipids.

2 Comments

  1. I saw Jahn present this work last week – I don’t think I’ve ever seen such a comprehensive analysis of any biological system. One thing that stuck in my mind is him casually flashing up a slide showing ~80 quantitative Western blots, all of which had been optimised and analysed by his post-doc Takamori (the first author on this paper). When he reached the 3D model of the vesicle and started rotating it on-screen there was an audible gasp from the audience. This is truly inspiring science.

  2. Yes. When I read it I remember thinking how fortunate for neuroscience that these competent molecular biologists have chosen the synaptic vesicle as the model vesicle.

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