Researchers at the Okinawa Institute of Science and Technology (OIST) have made a significant breakthrough in understanding the survival and pathology of sensory neurons. The team of neurobiologists discovered a link between the transport of messenger RNAs (mRNAs) within sensory neurons and their overall health.
The study focused on the dynein protein complex, specifically the Dynein Roadblock 1 (Dynlrb1) subunit, which is critical for the survival of neurons and the transport of vital molecules inside them. The researchers found that disturbances in the Dynein Roadblock 1 can hinder the production of necessary proteins, potentially threatening neuron survival.
One fascinating discovery from the study was the role of FMRP (fragile X messenger ribonucleoprotein 1) in transporting mRNA. FMRP is related to specific neurodevelopmental and neurodegenerative diseases and plays a role in conserving energy for the neuron by transporting mRNA instead of proteins.
Neurons have long protrusions called axons, within which molecules like proteins, RNA, and organelles travel. The researchers likened this transport system to a network of highways and trucks. The trucks responsible for propelling cargo inside neurons are part of the dynein complex.
The team investigated the Dynein Roadblock 1, or Dynlrb1, to understand how it affects the ability of the “dynein truck” to move or carry cargo. They found that FMRP is part of the cargo transported by the dynein complex. This finding was particularly interesting as FMRP is related to neurodevelopmental and neurodegenerative disorders, including fragile X syndrome.
The researchers also discovered that the removal of Dynlrb1 causes FMRP to stall and accumulate in the cell bodies and axons of sensory neurons. When mRNA bound to FMRP gets trapped and cannot undergo translation into proteins, it could jeopardize neuron survival.
Understanding which proteins cannot be produced when Dynlrb1 is absent or malfunctioning is the next research question for the team. This information could lead to new therapeutic approaches for neurodegenerative diseases.
The findings from this study provide valuable insights into the transport mechanisms within sensory neurons and shed light on potential dysfunctions that may contribute to certain neuropathologies. By uncovering the role of mRNA transport and the influence of Dynein Roadblock 1 and FMRP, researchers have opened up new possibilities for future research and treatment options for neurological disorders.
The study, titled “FMRP Long-Range Transport and Degradation Are Mediated by Dynlrb1 in Sensory Neurons,” was published in the journal Molecular and Cellular Proteomics. The lead author of the study is Sara Emad El-Agamy, a Ph.D. student at OIST. The research was a collaborative effort between OIST’s Molecular Neuroscience Unit, Membranology Unit, and scientists from the Riken Institute.