Neurons HOLD COFFEE Shop Conversations
Study reveals that individual neurons combine various RNA modifications of a crucial synapse protein.
In the bustling world of neural connections, each neuron serves as a chatty participant, engaging with fellow neurons, muscles, or other cells. They chat it up by releasing neurotransmitter chemicals at "synapse" junctions, resulting in a myriad of functions ranging from emotions to motions. However, even neurons of the same type can have vastly different chitchats. A new study published in Cell Reports by neurobiologists at The Picower Institute for Learning and Memory reveals a molecular mechanism that might account for this nuanced difference in neural discourse.
Troy Littleton's lab, housed within MIT's departments of Biology and Brain and Cognitive Sciences, focuses on how neurons regulate neurotransmitter release. In their lab, they frequently notice that individual neurons vary in their conversation styles — some "talk" more than others. Over a decade of investigations, Littleton's lab has found that a protein called complexin plays a critical role in limiting spontaneous chatter. It keeps the lid on the fusion of glutamate-filled vesicles at the synaptic membrane to preserve the neurotransmitter supply for when the neuron truly needs it to perform tasks, like stimulating a muscle to move.
In flies, the lab has uncovered two different types of complexin — and in mammals, there are four! The effectiveness of the rarer but powerful 7B splice form is regulated by a molecular process called phosphorylation. But the regulation of the much more common 7A version was a mystery. Research had shown that the RNA transcribed from DNA that forms the protein is sometimes edited in the cell by an enzyme called ADAR.
In this new study, Littleton's team, led by Elizabeth Brija, investigated whether RNA editing of complexin 7A affects how it controls glutamate release. What they discovered was mind-blowing. Not only does RNA editing impact the protein's ability to prevent glutamate release, but this can also vary wildly among individual neurons because they can randomly mix and match up to eight different versions of the protein. Some edits were more common than others on average, but 96 percent of the 200 neurons they examined had some editing that affected the structure of an end of the protein called its C-terminus. Experiments showed that different complexin 7A versions could dramatically change the level of electrical current measurable at different synapses. This varying level of activity could also affect the growth of synapses the neurons make with muscles. RNA editing of the protein might, therefore, give each neuron a unique communication style.
Littleton mused, "What this offers the nervous system is that you can take the same transcriptome and by alternatively editing various RNA transcripts, these neurons will behave differently."
The team found that other key proteins involved in synaptic glutamate release, such as synapsin and Syx1A, are also edited at different levels among the same population of neurons. This suggests that RNA editing might fine-tune several aspects of synaptic communication.
RNA editing can modulate the nucleotide sequence of RNA molecules, potentially altering protein function. In the context of neural function, RNA editing can affect synaptic transmission and neural plasticity by altering proteins involved in neurotransmitter release and receptor function. While specific details on complexin 7A RNA editing are not readily available, complexins are known to regulate synaptic vesicle fusion and neurotransmitter release. If RNA editing of complexin 7A alters its function, it could potentially affect glutamate release efficiency or kinetics, contributing to the diversity of neural circuits and behaviors.
More research is required to delve into the intricacies of complexin 7A RNA editing and its impact on neural discourse diversity. This would involve studying the molecular mechanisms of RNA editing in complexin 7A, its effect on glutamate release, and how these changes shape neural network functions.
- The study published in Cell Reports by neurobiologists at The Picower Institute for Learning and Memory focuses on neurotransmitter release and the nuanced differences in neural discourse.
- Neurons regulate neurotransmitter release, with a protein called complexin playing a critical role in limiting spontaneous chatter.
- Investigations by Troy Littleton's lab, housed within MIT's departments of Biology and Brain and Cognitive Sciences, have found that a protein called complexin varies in its regulation among individual neurons.
- The RNA transcribed from DNA that forms the protein complexin 7A is sometimes edited in the cell by an enzyme called ADAR, and this variation affects how the protein controls glutamate release.
- In this new study, Littleton's team discovered that RNA editing of complexin 7A impacts the protein's ability to prevent glutamate release and this can vary wildly among individual neurons.
- The varying level of activity caused by RNA editing could affect the growth of synapses the neurons make with muscles, potentially shaping neural network functions.
- RNA editing can modulate the nucleotide sequence of RNA molecules, potentially altering protein function, which can affect synaptic transmission and neural plasticity.
- This new research opens up possibilities for understanding the molecular mechanisms of RNA editing in complexin 7A and its impact on neural discourse diversity, which could pave the way for future studies in health, medicine, and mental science.
- With further investigation, experts may uncover new insights into neurological disorders, health-and-wellness, fitness-and-exercise, nutrition, and healthy-diets associated with complexin 7A RNA editing and its effects on neural discourse.
