In a race for what has been called the "holy grail" of molecularneurobiology, Japanese researchers have cloned a moleculethat receives nerve signals carried by the excitatorytransmitter glutamate.
Glutamate carries signals that govern memory and braindevelopment, as well as the unbridled neuronal activity thatcan cause epilepsy, the damage caused by stroke and thedegenerative changes of diseases such as Alzheimer's. Severalof its docking sites have been cloned, but an important holdout,called the NMDA receptor, has now been copied and reproducedin a Kyoto University laboratory.
Repeated failures to clone this cell surface receptor havesuggested that the molecule was made of different proteinsubunits. But the Kyoto scientists, writing today in Nature,showed that the single protein that they cloned can function infrog eggs with electrophysiologic and pharmacologiccharacteristics similar to those of the naturally occurringreceptor in rat brains.
The deduced amino acid sequence of the receptor's proteinshows marked similarities to the sequence of anotherglutamate receiver, the AMPA/kainate receptor that hadpreviously been cloned.
Discrepancies still persist in the data of labs studying theNMDA receptor, and the Kyoto researchers concluded thatsubtypes of the receptor are likely to exist. Indeed, anotherreport in Nature details the purification and reconstitution ofwhat appears to be a glutamate binding protein thatresearchers from the University of Kansas in Lawrenceconclude "is a subunit of the brain NMDA receptor."
In an accompanying editorial that hails the cloning as the "holygrail of neurotransmitter receptor molecular neurobiology,"National Institutes of Health researcher Mark Mayer wrote thatthe Japanese data "leaves little doubt" that they have isolateda genuine NMDA receptor.
"In contrast," Mayer said, "one wonders if the glutamate-binding protein isolated by (the Kansas group) could have someother function" apart from a role in forming the NMDA receptorchannel.
Several biotech companies are building therapeutic programsthat target the NMDA receptor, including Nova PharmaceuticalsCorp. (NASDAQ:NOVX) of Baltimore and Cortex PharmaceuticalsInc. (NASDAQ:CORX) of Irvine, Calif.
-- Roberta Friedman, Ph.D. Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.