Researchers from Kobe University have made a groundbreaking discovery in the field of neuroscience. They have identified a crucial protein, FAM81A, that plays a pivotal role in forming postsynaptic protein agglomerations, which are essential for synaptic function in the brain. This discovery not only contributes to our understanding of synaptic mechanisms but also opens new avenues for exploring the evolution of cognitive functions in higher vertebrates and potential implications for neuropsychiatric conditions.
The synapse, the connection between two neurons, is a key factor in brain function. The transmission of signals from the presynaptic to the postsynaptic neuron is mediated by proteins. Any imbalance in these proteins can lead to neuropsychiatric conditions such as severe depression, autism, or alcohol dependence. However, due to the vast diversity of proteins present at the synapse, many have not yet been studied, and it is often unclear whether previously identified proteins actually belong there or are just impurities resulting from the analysis process.
To shed light on this issue, the research team led by neurophysiologist TAKUMI Toru compared 35 datasets from previous studies on the postsynaptic density, a structure underneath the postsynaptic membrane that consists of thousands of different proteins. Through their analysis, they identified a poorly characterized synaptic protein, FAM81A, that appeared consistently in more than 20 of these datasets. This suggested that FAM81A is relevant to the function of the entire structure.
Further analysis revealed that FAM81A interacts with at least three major postsynaptic proteins and modulates their condensation. This interaction leads to the formation of a membrane-less organelle through liquid-liquid phase separation, a process in which strongly interacting molecules exclude elements of the surrounding medium. The absence of FAM81A leads to a significant decrease in activity in cultured neurons.
Interestingly, humans have two related copies of the gene, FAM81A and FAM81B. While FAM81A is expressed in the brain, FAM81B is expressed only in the testes. Birds and reptiles also have two copies of the gene, but amphibians, fish, and invertebrates have only one, and its expression is not localized to one tissue. This suggests that FAM81A could be a key protein in understanding the cognitive functions of higher vertebrate brains.
However, the researchers emphasize that their work is only the first step. To truly understand the role of FAM81A, further studies are needed to examine its function in the complex environment of the brain. The research team plans to create mouse models that lack the gene for FAM81A and study the impact on synapse function and organism behavior.
This groundbreaking research was conducted in collaboration with researchers from the University of Edinburgh, Kyoto University, and the University of Sheffield. The study was supported by grants from the Japan Society for the Promotion of Science and the Japan Science and Technology Agency.
In conclusion, the discovery of FAM81A as a crucial protein for synaptic function in the brain is a significant breakthrough in neuroscience. This protein’s interaction with major postsynaptic proteins and its involvement in liquid-liquid phase separation highlight its importance in maintaining synaptic activity. The findings not only contribute to our understanding of synaptic mechanisms but also have implications for the evolution of cognitive functions in higher vertebrates and potential implications for neuropsychiatric conditions. Further research is needed to fully understand the role of FAM81A and its impact on brain function and behavior.