Brain News – American researchers show how the FMRP protein in neurons works differently in its dendrites and nucleus. However, the dual FMRP functioning comes together to aid cognitive learning related to learning and memory.
Researchers at the Rockefeller University explored the different functioning of the FMRP protein in the memory neurons in the hippocampus region of the brains of mice. They micro-dissected synapses and cell bodies of these mice-neurons. Then, using techniques called “CLIP” and “TRAP”, they froze protein RNA-complexes in their places to analyze the composition of the dissected parts.
The findings, published in eLife, show how FMRP binds itself to different sets of RNAs in different parts of the neurons, namely, the dendrites (or neuron’s extensions) and the cell body. This makes it function differently in the two neuronal sections and collectively aid cognitive development related to learning and memory.
In the dendrites, FMRP is produced and bound to specific RNAs that influence synaptic responses. It acts like a switch—regulating the RNA sequences and modifying the strength of synapses—whenever a memory is being formed, remembered, or forgotten. It increases a neuron’s synaptic response by establishing a feedback loop between the dendrites and between the neuron’s nucleus.
Inside the cell body, FMRP binds itself to a different set of RNAs that are linked to chromatin modifiers or proteins that attach themselves to DNA and regulate the gene expression inside the nucleus of a neuron.
The dual FMRP functioning actually reveals—in the words of the lead researcher, Robert B. Darnell—how “The system [of a neuron] is built to contain itself.”
This study is significant because it highlights the role of the overlooked FMRP protein in brain functions. The researchers are enthusiastic that the findings can help develop learning and memory tools that effectively treat conditions like intellectual disability, fragile X syndrome, and autism.
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Hale, C. R., Sawicka, K., Mora, K., Fak, J. J., Kang, J. J., Cutrim, P., Cialowicz, K., Carroll, T. S., & Darnell, R. B. (2021). FMRP regulates mRNAs encoding distinct functions in the cell body and dendrites of CA1 pyramidal neurons. eLife, 10, e71892. https://doi.org/10.7554/eLife.71892