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.
Meanwhile, Worley’s team proceeded to build on research showing that a protein linked to a form of mental retardation passed on by an abnormal “fragile X” chromosome also represses the manufacture of some proteins. The researchers looked at Arc protein levels in nerve cells lacking the fragile X mental retardation protein and found stable levels of Arc protein all the time, before, during, after and even without stimulation of the nerve cells. They concluded that without fragile X protein, the presumed “brakes” on the system, the manufacture of Arc goes unregulated.
“It’s sort of a seesaw relationship,” Worley says. When nerve cells are stimulated, eEF2K is activated to suppress protein manufacture generally, thereby allowing for the rapid manufacture of Arc, and, at the same time, fragile X mental retardation protein is stimulated to let Arc protein get made.
“By defining a mechanism that is associated with fragile X syndrome — the most common inherited cause of mental retardation and autism — it may help others to identify potential therapeutic targets to help with the disease,” Worley says.
The research was funded by the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute on Aging.
Authors on the paper are Sunjin Park, Joo Min Park, Sangmok Kim, Jin-Ah Kim, Jason D. Shepherd, Constance L. Smith-Hicks, Shoaib Chowdhury, Walter Kaufmann, Dietmar Kuhl, Alexey G. Ryazanov, Richard L. Huganir, David J. Linden, and Worley, all of Hopkins.
Maryalice Yakutchik | Newswise Science News
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences