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50-year-old Mystery Solved: Protein Tags Regulate Key Ion Channel

Researchers at the University of Chicago have found that a recently discovered biological process known as sumoylation -- until now thought to be active only in the nucleus -- also occurs near the cell's surface where it regulates at least one and possibly many kinds of proteins, providing a novel target for the development of new drugs.

The discovery, published in the 8 April 2005 issue of the journal Cell, answers a question dating back to the 1950s: How do cells control the background movement of potassium ions across the cell membrane? This process is important because the flow of potassium ions determines whether "excitable" cells in the brain, heart and skeletal muscles "fire," sending out nervous impulses that become thoughts, heartbeats and basketball dunks.

"We found that a little-studied process called sumoylation, previously associated with nuclear proteins, is active and essential outside the nucleus at the plasma membrane," said study author Steven Goldstein, M.D., Ph.D., professor and chairman of pediatrics and director of the Institute for Molecular Pediatric Sciences at the University of Chicago. "This adds a new chapter to the book of how cells control ion channel function: reversible peptide linkage."

Ion channels are in every cell in the human body. They are tightly controlled tunnels through the membrane barriers that hold in the cell's contents, separating the cell from the outside world. Ion channels allow ions such as potassium, sodium and calcium to flow in and out and so are key regulators of many fundamental processes in biology.

"Ions are the currency of the cellular world," explained Goldstein. "Cells collect some ions, others they discharge. Ions are stored, spent, and exchanged."

"Cellular solvency," he added, "the ability to respond to the stimuli that are life, is all about the balance between ions inside and outside each cell. The gradual doling out or sudden influx of ions through ion channels
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Source:University Of Chicago Medical Center


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