Dartmouth Medical School

For Release: September 27, 2007
Contact: DMS Communications 603-650-1492

Flexibility Helps Cells Build Nuclear Passageways

HANOVER, NH—Like an athlete, a cell at work requires agility—at least for tunneling to the nucleus with its mother lode of genetic information, DMS biochemists report. Their research sheds light on the dynamics of building nuclear pores—the gateways for traffic to and from the nucleus, sometimes called the brain of the cell.

"We have identified a protein that helps the assembly process by regulating the flexibility of the nuclear membrane," said Dr. Charles Cole, professor of biochemistry and of genetics, who headed the research team. The work was published in the Journal of Cell Biology August 27, where it was compared it to loosening up for yoga. "Staying limber is crucial not just for yoga enthusiasts, but for cells installing nuclear pores," said the journal highlights.

The nucleus at the cell's core is well insulated with a protective, yet porous membrane envelope. To enter or exit the nucleus molecules pass through conduits called nuclear pore complexes, vast aggregations of proteins that span the envelope. The sheer size of the protein complexes—among the cell's largest—make it challenging to study, so many details of constructing the channels are yet to be worked out.

The DMS team focused on a yeast protein called Apq12 that helps export the RNA genetic material from the nucleus, interacting with components of the nuclear pore. The transport process misfires in yeast without the protein.

Yeast missing Apq12 were sensitive to cold, the investigators found. Low temperatures disrupted nuclear pore assembly, which interfered with cell growth. Warming the mutant cells suppressed the defect and the cells could again craft proper pore complexes.

Unlike their counterparts, the protein-deficient cells at low temperatures could not maintain their nuclear membrane fluidity, which the scientists determined was needed to assemble nuclear pore complexes. Exposing the cells to benzyl alcohol to help relax the membrane restored normal nuclear pore assembly, they demonstrated, confirming the crucial role of Apq12 in maintaining membrane flexibility.

Coauthors are John J. Scarcelli, a former graduate student and now a postdoctoral fellow, and Christine A. Hodge, a research assistant, both of biochemistry.

-DMS-