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
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Life Sciences
28.03.2017 | Information Technology
28.03.2017 | Physics and Astronomy