U.Va. researchers identify switching action by protein 'gate-keepers' in cell nucleus

CHARLOTTESVILLE, Va., August 9 A switching mechanism that controls the entry of proteins into cell nuclei, where genetic material is stored, has been identified by researchers at the University of Virginia Health System, according to study results published in today's issue of the journal Cell.

"The paper marks an advance in our understanding of how cells sort molecules that are to be sent to different places inside the cell," said principal investigator Ian G. Macara, professor of pharmacology at the U.Va. Markey Center for Cell Signaling.

"We call the molecules that are being moved around the cell 'cargo,' and each type of cargo has a Zip code attached that determines the address within the cell to which it must be delivered. We study proteins called 'importins,' which are like trucks that carry the cargo into the center of the cell, the nucleus," he said. "We have discovered a new component of one of these trucks that helps load the cargo, and ensures correct delivery. It may also help the truck distinguish among different nuclear entry codes."

The nucleus of a cell is surrounded by a wall that separates the DNA from the rest of the cell. This wall contains thousands of tunnels, called pores, through which the trucks and their cargo travel. Millions of cargo molecules are carried in and out of each nucleus every minute. This heavy traffic of proteins through the wall occurs in every living organism except bacteria.

Understanding the details of how things get in and out of the nucleus is important, Macara said, because viruses such as HIV have stolen the cargo codes and use the trucks to move their components in and out of the nucleus. This allows them to take control of the cell and to replicate within it.

The U.Va. study found that the new component, called Npap60 (nuclear pore-associated protein) attaches to its truck in three different ways, depending on whether the truck is in the cytoplasm picking up cargo, en route

Contact: Catherine Wolz
University of Virginia Health System

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