GSK3b regulates Gephyrin

The place where two neurons meet to pass on information is called a synapse. This passage of information is important for our brains to function properly.

To ensure that this communication is efficient, there are proteins in our brains called scaffolding proteins that act like anchors for the receptors and signaling molecules at the synapse. These proteins help to keep everything in the right place, so that the neurotransmitters can be effectively passed on.

We know a lot about how these proteins work in one type of synapse called glutamatergic synapses, but not as much about how they work in another type called GABAergic synapses. GABAergic synapses help to reduce or “inhibit” communication between neurons in the brain.

In this study, the researchers focused on a specific scaffolding protein called gephyrin that is important for GABAergic synapses. They found that phosphorylation of Gephyrin at the position Ser270 is done by glycogen synthase kinase 3β (GSK3β) to change how well it works.

When they stopped this process from happening, they found that there were more clusters of the gephyrin protein in the synapse, which increased the frequency of communication between the neurons. They also found that a drug called lithium chloride, which is used to help stabilize moods, can cause more gephyrin to cluster at the synapse.

However, they also found that another process called cleavage, which can break down proteins, can limit how much gephyrin is available to help with this communication.

Overall, this study helps us to understand how the gephyrin protein works at the synapse and contributes to the communication between neurons. It also suggests that the drug lithium chloride may work by changing how this protein works, which could be important for treating certain brain disorders.