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 OMRF 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.
“Dr. Miller’s research presents a new idea about how neurons control the location of their organelles,” said Michael Sesma, Ph.D., of the National Institutes of Health’s National Institute of General Medical Sciences, which partly supported the work. “By visualizing organelle movement in neurons using living, see-through worms, we are better able to understand how human brain cells develop and respond to injury.”
“We’re a long way from using this discovery for treatment, but this kind of basic research is essential to moving the ball forward,” said OMRF President Stephen Prescott, M.D. “New tests and therapeutics won’t arrive unless we lay the groundwork by understanding the fundamentals of how brain cells develop and work.”
C. elegans may continue to play an important role in understanding how brain cells function. Earlier this month, President Obama announced a $100 million BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative with a goal of making breakthroughs akin to the Human Genome Project of the 1990s. He has appointed a C. elegans neurobiologist to co-chair a committee for how best to direct funding.
The study was a collaboration with Janet Richmond, Ph.D., at the University of Illinois, Chicago. OMRF researchers Stacey Edwards, the lead author, and Christopher Hoover, as well as former OMRF researcher Barret Phillips, also participated in the project.
The research was funded by grant No. GM080765 from the National Institute of General Medical Sciences and No. MH073156 from the National Institute of Mental Health, part of the National Institutes of Health.