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27.03.2021 15:57
On the trail of the messenger
Scientists track mRNA molecules and newly synthesized proteins within living nerve cells
Neurons communicate over long distances and form remarkably complex and intertwined networks. Their processes, dendrites and axons, are between hundreds of micrometers and up to a meter long and create up to tens of thousands of connections, synapses, with other brain cells. It is believed that strengthening or weakening these connections, called “synaptic plasticity,” is an essential part of our ability to learn and remember. An important feature of synaptic plasticity is a rapid and dynamic change in the proteins present at the synapses. Given the great distances that these cells cover, the rapid supply of proteins to the distant areas is a major logistical challenge. Neurons solve this problem in part by positioning the blueprints for proteins (mRNAs, the messengers) in their dendrites and axons – and thus giving the cell the opportunity to produce proteins on site as required.
While thousands of mRNAs are located in distant locations within neurons, little is known about how they get to those distant locations and how they behave during synaptic plasticity. To close this knowledge gap, a team of scientists led by Erin Schuman, Director at the Max Planck Institute for Brain Research, and the Heckel Laboratory at Goethe University (Frankfurt) developed a strategy for marking and tracking neuronal mRNAs in living neurons. Using a special “molecular beacon” for binding individual mRNAs and (using) high-resolution microscopy in living neurons, they tracked and assessed how three different mRNAs are transported within dendrites.
“We found remarkably similar motions for individual mRNAs, suggesting a common method of controlling their delivery to remote locations,” says Paul Donlin-Asp, the postdoc who led the work. “The creation of two different forms of synaptic plasticity, one strengthening the connections between neurons and the other weakening them, caused the mRNAs to move less and to cluster near the synapses. This suggests that the Synapses that pick up mRNAs to produce new proteins, “explains Donlin-Asp.
Using a variety of strategies to monitor the production of the proteins encoded by these mRNA blueprints, the scientists found that changes in the behavior of the mRNAs during synaptic plasticity do not necessarily result in a change in the production of the protein to lead.
“These results suggest that during synaptic plasticity, mRNAs are first” captured “in order to later convert them into protein,” says Schuman.
This study was supported by the Peter and Traudl Engelhorn Foundation, the Humboldt Foundation, the Max Planck Society, the European Research Council and the German Research Foundation.
Scientific contact:
Prof. Dr. Erin Schuman
Director
Max Planck Institute for Brain Research,
Frankfurt am Main
[email protected]
Originalpublikation:
Paul G. Donlin-Asp, Claudio Polisseni, Robin Klimek, Alexander Heckel, and Erin M. Schuman. Differential regulation of local mRNA dynamics and translation following long-term potentiation and depression. Proceedings of the National Academy of Sciences Mar 2021, 118 (13) e2017578118; DOI: https://doi.org/10.1073/pnas.2017578118
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