▎ WuXi AppTec content team editor
Every day-to-day behavior we do relies on a steady stream of signaling in the brain, and once the signals get out of control, a range of neurological disorders, from epilepsy to schizophrenia, can occur.
The various chemical molecules in the brain play a role in regulating signals. Recently, new research in Cell Reports has found two proteins, RIM1 and SRPK2, which are involved in brain signal regulation, which are mainly responsible for controlling signaling at synaptic sites.
Synapses act as a signal transit station, some signals can be transmitted downstream when they arrive, and some signals accumulate to a certain extent before they are transmitted. According to the new study, specific signals need to be released and which need to wait, relying on RIM1 to complete.
Key to this are the many synaptic vesicles in the synapse that are filled with neurotransmitters, which wait on the synaptic side and are released when the right signal is received. "The number of these synaptic vesicles released, as well as the response of the receptors to them, is tightly controlled," said Dr. Schoch McGovern, a neuroscientist at the University of Bonn in Germany.
Dr. McGovern and colleagues have found in fruit flies that RIM1 is more active in this process. Still, it remains unclear whether more advanced organisms will have more complex regulatory mechanisms. To that end, he and his colleagues extended the study to the mouse level.
▲SPRK2 will modify RIM protein to affect synaptic signaling process (Image source: Reference[2])
In the analysis of the new study, they found that during the release of synaptic vesicles, an enzyme called SRPK2 continuously adds phosphate groups to some amino acids of RIM1, and correspondingly, phosphorylation of specific amino acids increases the number of synaptic vesicles released.
"Whether to increase or decrease the number of synaptic vesicles depends on which amino acids are phosphorylated," Dr. McGovern explains. They don't yet know how the phosphorylated RIM1 will be treated after it performs its functions, and it is possible that other enzymes will modify it to complete subsequent regulation.
According to the findings in mice, RIM1 has the potential to be a therapeutic target for many neurological disorders, especially those caused by signaling disorders.
Resources:
[1] Scientists Find an Enzyme That May Stop Brain Activity Getting Out of Control. Retrieved Apr 25th, 2022 from https://www.sciencealert.com/proteins-that-keeps-your-brain-under-control-could-help-explain-various-disorders
[2] Johannes Alexander Muller, Julia Betzin, et al. A presynaptic phosphosignaling hub for lasting homeostatic plasticity. Cell(2022), DOI: 10.1016/j.celrep.2022.110696
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