Scientists find an enzyme that can prevent brain activity from getting out of hand

Our brains are flooded with various unsung chemical heroes, keeping the electrical signals going everywhere from getting out of hand.

A new mouse study has now detailed the function of a few proteins essential to maintaining this balance — this could help us better understand a range of neurological disorders, from epilepsy to schizophrenia.

The two proteins — Rab3-interacting molecule 1 (RIM1) and an enzyme called serine-arginine protein kinase 2 (SRPK2) — work together to alter the transmission of information about the gaps between nerves called synapses.

Without their efficient control of neural activity, messages could either be lost due to insufficient signal, or flood important nodes, overwhelm important networks and bury important signals in a cacophony of noise.

Using neurons from specially prepared laboratory mice, researchers from Germany and Australia have now described in detail the precise chemical interplay between the two proteins, which not only helps us better understand typical brain function, but could one day provide therapeutic targets for conditions in which this process goes wrong.

Synapses can be thought of as transportation terminals that connect commuters in your brain to different services. Some services depart as soon as a handful of passengers arrive; others wait to be hit by a wave of commuters.

Like any efficient public transport system, this passenger flow needs guidance on when to wait and when to board. That’s where RIM1 comes in.

Instead of commuters waiting at the station, neurons have tiny bubbles filled with transmitters on the verge of release at the synapse, ready to pour out as soon as a suitable signal arrives.

“However, the amount of neurotransmitter released by the presynapse and the degree to which the postsynapse responds to it is strictly regulated in the brain,” says neurologist Schoch McGovern of University Hospital Bonn, Germany.

Much of what we know about this regulation is based on relatively simple organisms. For example, it was by studying the larvae of fruit flies that researchers noticed the activity of RIM1.

It’s likely that more complex animals have different mechanisms that help refine their own brains, so researchers analyzed the mechanisms of the protein extracted from mouse brains to see how it worked.

They found that the enzyme SRPK2 modifies RIM1 by adding molecules with phosphate groups to specific links of the amino acid structure, increasing or decreasing the number of neurotransmitter bubbles released at the synapse.

“Which effect occurs depends on the phosphorylated amino acid,” says Johannes Alexander Müller, neurophysiologist at University Hospital Bonn.

What happens to the phosphorylated RIM1 proteins after they do their job isn’t clear, leaving room for a range of other enzymes to further refine the process.

As with any biological function, it can be just as helpful to know what’s happening when things don’t go according to plan. There is already genetic evidence that RIM1 could be involved in conditions such as autism and schizophrenia.

“We now want to further elucidate these relationships,” McGovern says.

“Perhaps in the long term, new therapeutic options for these diseases will emerge from our findings, although there is certainly a long way to go before that happens.”

This research was published in Cell

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