Neuroscience Breakthrough: Researchers Uncover Key Protein Complex for mRNA Delivery in Brain Cells
A significant breakthrough in neuroscience research has unveiled a protein complex that plays a vital role in transporting messenger RNA (mRNA) within neurons. Collaborative efforts from teams at the Max Planck Institutes in Dresden, Dortmund, Frankfurt am Main, and Göttingen have led to the identification of this complex, shedding light on an essential missing link in the understanding of mRNA distribution in brain cells.
Proteins are crucial for every aspect of brain cell functioning, and disruptions in their production can lead to severe neurological disorders such as epilepsy and disability. The teams, led by Marino Zerial from the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden and Stefan Raunser from the Max Planck Institute of Molecular Physiology in Dortmund, have made significant progress in this area. Working alongside colleagues from the Max Planck Institutes for Brain Research in Frankfurt am Main and Biophysical Chemistry in Göttingen, they have discovered a novel mechanism that precisely transports mRNA, the blueprint for proteins, to the required destinations within neurons.
Using a variety of techniques, the researchers have identified a protein complex named FERRY, which acts as a connection between mRNA and intracellular carriers. They have also elucidated its structure and function. This groundbreaking discovery holds the potential to deepen our understanding of neurological disorders stemming from malfunctioning FERRY and may open up new avenues for medical intervention. The results of their study have been published in two consecutive papers in the journal Molecular Cell.
FERRY, when linked to Early Endosomes (EEs) in neurons, functions akin to a secure strap during transportation. It directly interacts with mRNA and firmly holds it onto EEs, thereby transforming them into logistic carriers responsible for mRNA distribution and transport within brain cells.
“These publications represent a significant advancement in unraveling the mechanisms underlying mRNA distribution in brain cells,” stated Marino Zerial, emphasizing the importance of these findings.
Within brain cells, a logistical challenge arises due to their tree-like structure, with branches extending over considerable distances. Thousands of mRNAs need to be transported far away from the nucleus, comparable to the task of adequately supplying supermarkets across an entire country, as explained by Jan Schuhmacher, the study’s lead author.
Until now, researchers believed that Late Endosomes, spherical compartments within cells, played the primary role as carriers. However, the Max Planck Institute scientists argue that Early Endosomes (EEs), a different form of compartments capable of traveling in both directions along intracellular networks, are also suitable as mRNA carriers. The first publication, led by Marino Zerial from the Max Planck Institute in Dresden, reveals the function of the newly identified protein complex, FERRY. By understanding how FERRY binds to mRNA, the second publication led by Stefan Raunser’s group from the Max Planck Institute in Dortmund employed cryo-electron microscopy to determine the structure of FERRY and its molecular features responsible for binding to both EEs and mRNAs. Additionally, the scientists shed light on how certain genetic mutations can hinder FERRY’s ability to bind mRNA, consequently leading to neurological disorders.
“Our research lays the foundation for a more comprehensive understanding of neurological disorders resulting from mRNA transport or distribution failures and may contribute to the identification of therapeutically relevant targets,” stated Stefan Raunser.
- “Structural basis of mRNA binding by the human FERRY Rab5 effector complex” by Dennis Quentin et al., Molecular Cell, June 1, 2023. DOI: 10.1016/j.molcel.2023.05.009
- “The Rab5 effector FERRY links early endosomes with mRNA localization” by Jan S. Schuhmacher et al., Molecular Cell, June 1, 2023. DOI: 10.1016/j.molcel.2023.05.012
Frequently Asked Questions (FAQs) about mRNA transport
What is the significance of the recent neuroscience breakthrough regarding mRNA delivery in brain cells?
The recent neuroscience breakthrough regarding mRNA delivery in brain cells is highly significant as it unveils a protein complex called FERRY, which plays a crucial role in transporting messenger RNA (mRNA) within neurons. This discovery provides a missing link in understanding how proteins are produced in brain cells and offers insights into the mechanisms underlying neurological disorders caused by mRNA transport malfunction.
How does FERRY function in mRNA transport within neurons?
FERRY functions by linking mRNA to Early Endosomes (EEs) in neurons. It acts as a tie-down strap during transport, directly interacting with mRNA and securely holding it onto EEs. This transforms the EEs into logistic carriers responsible for the distribution and transport of mRNA within brain cells.
What are the potential implications of this research for neurological disorders?
The research on FERRY and mRNA transport holds promising implications for neurological disorders. By understanding how FERRY binds to mRNA and the structure of the protein complex, scientists can gain insights into how genetic mutations affecting FERRY can lead to neurological disorders. This knowledge may contribute to identifying therapeutically relevant targets and developing potential treatments for these disorders.
Which institutions and researchers were involved in this breakthrough?
Collaborative efforts from teams at the Max Planck Institutes located in Dresden, Dortmund, Frankfurt am Main, and Göttingen led to this breakthrough. Marino Zerial from the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden and Stefan Raunser from the Max Planck Institute of Molecular Physiology in Dortmund were the lead researchers. Colleagues from the Max Planck Institutes for Brain Research in Frankfurt am Main and Biophysical Chemistry in Göttingen also played significant roles in the study.
Where can I find more information about this research?
Further information about this research can be found in the two recent publications in the journal Molecular Cell. The first publication is titled “The Rab5 effector FERRY links early endosomes with mRNA localization” by Jan S. Schuhmacher et al., and the second publication is titled “Structural basis of mRNA binding by the human FERRY Rab5 effector complex” by Dennis Quentin et al.
More about mRNA transport
- Molecular Cell – “The Rab5 effector FERRY links early endosomes with mRNA localization”
- Molecular Cell – “Structural basis of mRNA binding by the human FERRY Rab5 effector complex”