In nerve cells, just as in real estate, it's “location, location, location.” Organelles are specialized structures with specific roles within the cell. A scientist from the Oklahoma Medical Research Foundation has uncovered a gene responsible for making sure the location of organelles inside nerve cells doesn't interfere with their vital ability to send and receive messages.
In a paper published and highlighted with a commentary in the latest issue of the journal Genetics, OMRF researcher Kenneth Miller, Ph.D., describes how unc-16, a gene humans share with tiny roundworms called C. elegans, may act as a “gatekeeper” in nerve cells to keep organelles from moving to the wrong location.
“Nerve or brain cells are a lot like other cells in the body, in that they have internal membrane-bound organelles — including mitochondria, Golgi and lysosomes — which are critical for the cells to function,” Miller said. “But unlike other cells, they also have long extensions protruding from their bodies that allow them to talk to other nerve cells throughout the body.”
One kind of extension is the “axon,” which is incredibly complex and is used to communicate with other nerve cells and muscle cells. For years, scientists have wondered why the organelles in the neuron's cell body don't invade the long axon, which could disrupt those communications.
Using a method called “forward genetics,” Miller's lab was able to identify mutant worms in which organelles accumulated in the axon by tagging the organelles with fluorescent proteins. This allowed them to see the organelles through the microscope in living animals.
They then mapped the mutations to the unc-16 gene. “‘Unc' is short for uncoordinated, meaning these worms don't move very well. We think the clogging of axons ultimately interferes with the signaling, which could contribute to their sluggishness,” Miller said.
In longer-lived animals, such as humans, clogged axons may cause neuronal degeneration. Indeed, genes with which unc-16 interacts are associated with neurodegenerative disorders in humans, such as hereditary spastic paraplegia and progressive lower motor neuron disease.
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We're a long way from using this discovery for treatment, but this kind of basic research is essential to moving the ball forward. New tests and therapeutics won't arrive unless we lay the groundwork by understanding the fundamentals of how brain cells develop and work.”
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