Researchers at the Johns Hopkins University School of Medicine report in the July issue of Neuron how nerve cells in the brain ensure that Arc, a protein critical for memory formation, is made instantly after nerve stimulation. Paradoxically, its manufacture involves two other proteins - including one linked to mental retardation - that typically prevent proteins from being made.
Previous research already established that long-term memory formation depends on Arc protein, but scientists did not know the mechanism that turned on this process.
To find it, they surveyed proteins in mouse brains that change or are activated after a nerve is stimulated and identified eEF2K (short for eukaryotic elongation factor 2 kinase) as a player. When turned on, eEF2K inhibits an important step of protein translation.
"This seemed strange, because it suggested that nerve cells might make Arc protein by using pathways typically thought to turn off protein manufacture," says Paul Worley, M.D., a professor of neuroscience in the Johns Hopkins University School of Medicine.
Further examination of mouse brain slices lacking eEF2K in their nerve cells showed that when stimulated, such cells fail to make the usual pools of Arc protein, demonstrating that eEF2K is required for making Arc.
What it didn't tell them was whether eEF2K specifically was responsible, or whether some other pathway is also involved, so researchers next treated the brain slices from normal mice with a chemical that inhibits protein manufacture by the same mechanism as eEF2K. At the same time that general protein synthesis was turned down, Arc translation actually increased, making it clear eEF2K, through its ability to turn down protein manufacture, somehow enabled a nerve cell to make Arc in response to nerve stimulation.