Protein studies reveal sophisticated control of nerve com...( yotiao tells us that its signaling con...)

Scott and other members of his team, including Lorene Langeberg and Iain Fraser, collaborated with members of HHMI investigator Morgan Sheng's laboratory at the Massachusetts General Hospital, describe their findings in the July 2, 1999 issue of the journal Science.

The story of yotiao's discovery began in the early 1990s, when Fraser isolated a small piece of DNA. "We had very little idea what it was," said Scott. But a better picture began to emerge as postdoctoral researcher Ryan Westphal with help from graduate student Neal Alto gradually isolated overlapping pieces of DNA, and regions of the sequence began to look familiar. That recognition led Scott and his team to their eventual identification of yotiao.

Since the early 1990s, Scott has focused his research on the process by which chemical signals from outside a cell are transported through the nerve cell membrane to particular locations within the cell, where they exert their biological effect. He is particularly interested in one such signaling pathway that activates an enzyme called cAMP-dependent protein kinase (PKA), and how nerve cells organize specialized pools of PKA so that these pools will be ready for instant use.

As it turns out, PKA is one of the two enzymes that yotiao holds near the NMDA receptors. Whenever the anchor protein releases it, PKA stimulates the channels to allow in more calcium ions.

Yotiao's other closely held enzyme, called type 1 protein phosphatase (PP1), has the opposite effect: it downregulates NMDA receptors, or slows the flow of ions. Steven Tavalin, an HHMI associate in Scott's laboratory, has shown that PP1 is also at work even while it is still bound to yotiao. The net effect, then, of yotiao and its two enzymes is that calcium is prevented from entering neurons at rest.

That constant blockade may sound curious at fi
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
2-Jul-1999