Popescu Lab Paper Recognized by Faculty of 1000

The article received two out of three stars — or a “very good” rating — from an evaluator with the post-publication peer review service.

The paper sheds light on processes involving the synaptic protein NMDA receptor, whose overactivity has been implicated in neurodegenerative conditions and mental illness.

Upon binding the neurotransmitter glutamate, this protein gates an ionic current across the cellular membrane, Popescu explains. The current is necessary for normal development of the central nervous system as well as learning and memory throughout life.

However, under certain conditions, such as stroke or ischemia, the NMDA receptor produces an enhanced current that leads to neuronal death.

The research addresses unknown questions about how currents are produced in response to glutamate binding and how this response can be modulated.

Popescu and her colleagues studied basic receptor properties in the protein’s C-terminal domain—one of two with recognition sites for neuromodulators.

When they produced and engineered receptors that lacked portions of their C-terminal tails, they found that truncated receptors had profoundly altered functions.

Using more selective truncations of the C-terminal domain, they determined that the N1 tail altered how much current each opening produced, whereas the N2 tail determined how much the receptor stayed open.

“This result clearly indicated that each N1 and N2 tail has distinct roles in controlling the NMDA receptor current,” notes Popescu.

“This is important because, in vivo, each of the N1 and N2 tails is modified by phosphorylation, and thus responds to intracellular cascades.”

Popescu’s paper “provides new insight into intracellular mechanisms of (NMDA) receptor modulation,” according to F1000 reviewer Robert Peoples, PhD, associate professor of biomedical sciences at Marquette University.

His full F1000 evaluation is available online.

Bruce E. Maki, a PhD candidate in neuroscience, is lead author on the paper, which was originally published in the Journal of Biological Chemistry.

Co-authors are Teresa K. Aman, a postdoctoral associate in biochemistry, and former PhD students Stacy A. Amico-Ruvio and Cassandra L. Kussius.

To be recommended for F1000 Prime, a research article has to have been recognized as being “of special excellence,” says senior managing editor Martin Delamare.

“Articles are selected for recommendation purely on the basis of their scientific merit and regardless of the journal in which they are published.”

F1000 prime highlights and recommends articles across biology and medicine based on the opinions of more than 5,000 expert scientists and clinical researchers.

The service subdivides biology and medicine into principal subject areas, including pharmacology and drug discovery.

“Each faculty has its own panel of peer-nominated experts who recommend the best of the literature relevant to their subject area,” Delamare says.