The Hidden Proteins in Your Brain
By: Gunnar De Winter
Tags: Technology, Health, Science, Neuroscience, Brain

The Hidden Proteins in Your Brain

A detailed look at synaptic vesicles identifies previously missed proteins

(Wikimedia commons, GerryShaw)

The talking brain

It is sometimes said that the human brain is the most complex known object in the universe.

Sure, that’s probably an anthropocentric delusion of grandeur. Still, the collection of hundreds of billions of brain cells with their trillions of connections is a difficult puzzle to put together.

Neuron anatomy. (Wikimedia commons, Jennifer Walinga)

For that complex structure to function properly, it needs to ensure smooth communication between its parts. The main workhorses in our brains are the neurons. These long spindly cells are specialized in cellular communication.

Neurons have a cell body (the soma) and the tree-like extensions of this body are known as dendrites. A very unique part of the neuron is the nerve fiber or axon, a long ‘cable’ than can extend for many hundreds or thousands of times the size of the soma. (The longest axon in the human body is that of the sciatic nerve and runs from our hips to our feet. You know how lower back pain can run all the way down your leg? Pinched sciatic nerve.)

Axons have a few traits that make them master communicators.

Synapse. (Wikimedia commons, Young, KA., Wise, JA., DeSaix, P., Kruse, DH., Poe, B., Johnson, E., Johnson, JE., Korol, O., Betts, JG., & Womble, M.)

For one, healthy axons are covered by a myelin sheath, a fatty insulating cover that speeds up the electrical impulses traveling along the axon.

Another communication tool of the axon can be found at its end. There, the axon branches out into many axon terminals. These terminals have synapses, the gaps between the ‘buds’ at the end one neuron and another neurons. Via this gap, the brain cells can pass on signals. They do this mainly via burping out chemicals called neurotransmitters. (There are also electrical synapses where the electrical current can zip through without needing chemicals.)

Decoding signals

The content of a neuron’s message depends on the neurotransmitters that are transferred (for chemical synapses).

These chemical messengers are gathered into synaptic vesicles which fuse with the cell membrane of the neuron. As a result, their contents are released into the synaptic cleft. Depending on the receptors embedded in the membrane of the receiving cell, the message is ignored or passed along.

Both the collection of receptors on the receiver cell and the content of the synaptic vessels in the transmitting cell can be very diverse. This is known as synaptic diversity.

Curious as we are (brains want to know themselves, after all), we would like to figure out the chemical brain messages that make us think and feel.

Fortunately, we’ve been able to identify plenty of neurotransmitters and their part in different messages.

Unfortunately, the protein machinery in the synaptic structures (for example, the proteins that ‘package’ the neurotransmitters) is not yet entirely resolved.

Looking closer

A new study now presents a new method to take a more detailed look at these synaptic proteins.

Previous methods used are a bit of a brute-force approach: take a bunch of synaptic material, run it through a mass-spectrometer and see which proteins you can identify. This is great and has helped us identify plenty of involved proteins. However, this mostly gives us the average protein composition, dominated by the most abundant proteins.

In the new study, the scientists used enzymes to ‘trim’ and ‘pre-digest’ the synaptic proteins in their samples (rat brain, in case you were wondering). Next, they separated all these protein chunks (peptides) and ran them through mass-spectrometers.

As a result, they were able to identify around 1,500 proteins involved in the synaptic vesicles, three times more then reported in previous studies.

Some of the previously missed proteins are involved in vesicle transport, neurotransmitter uptake, as well as still to be resolved mystery functions.

Interestingly, many of the proteins identified in this study, despite not being present in huge numbers, are thought to be involved in diseases such as epilepsy, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and cerebellar ataxia.

As the authors conclude:

This synaptic vesicle proteome revealed many proteins of physiological and pathological relevance, particularly in the low-abundance range, thus providing a resource for future investigations on diversified synaptic functions and neuronal dysfunctions.

Your brain is a busy place.