Protein shuttle service

Researchers have glimpsed two proteins working together inside living cells to facilitate communication between the cell’s nucleus and its exterior compartment, the cytoplasm. The research provides new clues into how a crucial protein that is found in organisms from yeast to humans does its work.

The study, led by Investigator Sue Jaspersen, PhD, focused on a protein called Ndc1, which controls when and where a cell inserts holes into the double-walled membrane that surrounds its nucleus. In yeast, these holes become the sites for two essential structures: passageways called nuclear pore complexes, and spindle pole bodies, which anchor the cytoskeletal filaments that pull chromosomes to opposite sides of a dividing cell. “Too many or too few insertion sites will have disastrous consequences,” Jaspersen says.

The Jaspersen team created yeast with mutations in the Ndc1 gene. As expected, changes that disrupted Ndc1’s interaction with its known partners in the nuclear core complex or the spindle pole body were lethal. One mutation puzzled the scientists, however. The altered Ndc1 protein bound to the expected components of both the nuclear pore complex and the spindle pole body, just like the normal protein. But when yeast cells produced this altered version of Ndc1, they died, suggesting another critical interaction partner.

Using a method to detect interactions at the nuclear envelope, the Jaspersen team found that Ndc1 bound to a protein called Mps3. Mps3 and Ndc1 came together in the nuclear envelope, but away from the two structures the team had set out to study. This led them to speculate that Mps3 might help shuttle Ndc1 to the sites where it is needed, controlling the distribution of nuclear pore complexes and spindle pole bodies. The Jaspersen team is now planning further experiments to test how Ndc1 and Mps3 maintain the appropriate balance of these critical structures.

The findings were published in the February 10, 2014, issue of the Journal of Cell Biology.