The molecule in question is called Luman, a nerve cell (neuron) protein discovered by Dr. Vikram Misra in the Western College of Veterinary Medicine while investigating the common cold sore virus. Luman is aptly named after a famous Chinese warrior, since it springs into action when neurons are stressed.
While the virus hides out in sensory neurons most of the time, Misra found that when it senses Luman, it knows something is wrong. Like a rat sensing that its ship is sinking, the virus re-emerges from the neurons and looks for an escape route — in this case producing a cold sore, ready to infect others.
Verge is a professor in the U of S College of Medicine and director of the Cameco MS Neuroscience Research Centre based at City Hospital in Saskatoon. She and Misra, together with PhD student Zhengxin Ying, wondered if Luman had a more general role in informing sensory neurons about stress events such as nerve injury.
Molecules such as Luman act like order sheets in a repair shop. When a nerve is injured, the order comes in from the site of injury to manufacture and send out proteins to make repairs. Luman goes to the cell nucleus, gets the cell's DNA to generate templates for the proteins needed for repair, then transfers these specs to the cell's protein factory — the endoplasmic reticulum (ER) — to build what is needed.
She explained that in sensory neurons, Luman's role is complicated by distance. Like other cells, neurons have a main body and, growing from this main body are axons — long, branching filaments that carry nerve impulses from cell to cell, all the way from the brain to the extremities and back. In the legs, axons can run from hip to toe.
To deal with this problem of distance, neurons have an ER in the main cell body and a version all along the axons. Analogous to repair shops along a highway, these axonal ER sites manufacture repair proteins close to the site of injury. The researchers discovered Luman hangs around until it becomes activated by a stress event such as an injury — and that the local ER can make more Luman to keep the signal going.
Verge said a series of novel experiments by Ying show Luman is not only an order taker, but also a messenger, shuttling information back to the nucleus of a neuron where it regulates events that are critical for re-growing the damaged axon.
"This is a brand-new concept, that all the way out in the axon there are molecules in the endoplasmic reticulum that can sense the stress of a nerve injury and send that signal back to the cell body to further regulate axon repair," she said. "This is another major piece of the puzzle (in understanding how nerves heal)."
Verge and her colleagues will now be looking to find out more about which Luman-regulated proteins and processes are the active players in repairing injured nerves. "We're now also in the lab looking at strategies and ways that might rev this (repair process) up," Verge said.
Verge, Misra and Ying's findings are published in the Proceedings of the National Academy of Sciences. The research was supported by funding from the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada.