Protein studies reveal sophisticated control of nerve communication

July 2, 1999 - With their discovery of a curious brain protein, named for a Chinese breakfast noodle, a team of HHMI investigators have provided a new understanding of just how exquisitely nerve cells control the electrical impulses they use to communicate with one another.

The protein yotiao (pronounced "YOH-tee-ow") anchors itself on the inner membrane of neurons in the hippocampus, a small brain region associated with learning and memory. Like other anchoring proteins, yotiao is an organizer whose purpose is to corral particular enzymes or other molecules that govern cell functions into specific "compartments" or pools within a cell. Yotiao itself is somewhat unusual in that it binds not one but two kinds of enzymes, both of which help regulate electrical signals that pass from neuron to neuron.

But "the really cool thing about yotiao," explained HHMI investigator John D. Scott, is that it holds the enzymes right next to their site of action -- a crucial type of receptor known as N-methyl-D-aspartate (NMDA) receptors. NMDA receptors nestle in the specific part of the nerve cell membrane where neurons communicate chemically with each other across a tiny gap known as a synapse. They are the principal channels through which positively charged calcium ions stream into the nerve cell. The rapid inflow of calcium and outflow of another ion, potassium, generates an electrical nerve signal.

"This is one of the first times, if not the first, that we've seen an anchor protein that physically attaches not only to signaling enzymes but also to their receptor," said Scott, whose laboratory is at the Vollum Institute of Portland's Oregon Health Sciences University. "That means the receptor has everything it needs absolutely at the right place, ready for action whenever it needs it.

"We've known that the cell is not just a bag of enzymes floating around," he continued. "But

Contact: Jim Keeley
Howard Hughes Medical Institute

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