Ribosomal Complex Visualized in Action in Nerve Cells

A team of researchers from Charité University in Berlin has successfully observed protein production by ribosomes in the developing brain. Their findings were published in Molecular Cell.

"It is the first time the ribosomal complex has been visualized in action inside the brain at near atomic-level resolution," says lead researcher Christian Spahn. "While the structure of the ribosomal complex has been mapped in other tissues and organisms, our approach enabled us to identify Ebp1 as the new key factor responsible for controlling both ribosome function and the synthesis of specific proteins during brain development." The interaction between the regulatory protein Ebp1 and the ribosome takes place at the ribosome's exit tunnel, through which the newly formed protein chain emerges from the ribosome. Through this interaction, Ebp1 influences the production of membrane proteins that play an important role in neuronal interactions, thus maintaining neuronal proteostasis.

As part of a multidisciplinary project linking aspects of structural biology and neuroscience, the researchers used cryo-electron microscopy as their main investigative tool, combining it with mass spectrometry, RNA sequencing and genetic techniques. The study's first author, Matthew L. Kraushar explains, "We could therefore visualize the molecular architecture of the ribosome at high resolution, as it would be found inside brain cells. We were able to capture snapshots of the ribosome in action."

"Protein production in various types of brain cells is subject to finely tuned control mechanisms. Small changes can lead to big consequences, such as neurodegenerative diseases or disrupted development. Our findings on the role of ribosomes during normal brain development will help us to better understand pathological changes affecting the brain," says Spahn. As a next step, the researchers are conducting a large-scale study to understand the way ribosomes translate messages from the genetic code (mRNA) into numerous essential proteins throughout brain development.