Forced cell rewiring sheds new light on cell division machinery

03 August 2015

An example of the plates used by the researchers to identify which forced protein-protein interactions still allowed the yeast to grow.

Image: An example of the plates used by the researchers to identify which forced protein-protein interactions disrupt or allow cells to grow.

Francis Crick Institute researchers have developed a way to systematically relocate every protein in a cell to test whether their location is critical for their function.

Dr Peter Thorpe of the Crick (currently based at Mill Hill) said: "The locations of proteins within cells are assumed to be critical for their function - but are they?

"We developed a technique that can test this by relocating every protein within a living cell - much like rewiring an electric circuit and and then testing whether it still works."

The scientists' method involves systematically fusing a target protein with each of the other proteins expressed by a cell. The resulting 'tug of war' can drag proteins to new locations within the cell and forces interactions between proteins that may not normally work together.

This allows researchers to then work out which of these forced interactions and relocations affect how the cell behaves.

As proof of principle, Dr Thorpe and his colleague Guðjón Ólafsson used this system in yeast to individually fuse all the yeast proteins to a component of the kinetochore - the cellular structure that pulls chromosomes apart as cells divide. This allowed them to identify which proteins were important in regulating the function of the kinetochore.

Dr Thorpe added: "This technology has the potential to relocate every protein to compartments all over the cell, and so find out how resilient the cell is to having the spatial arrangement of its proteins shuffled."

The paper, Synthetic physical interactions map kinetochore regulators and regions sensitive to constitutive Cdc14 localization, is published in Proceedings of the National Academy of Sciences.

  • Francis Crick Institute researchers have found a way to test the theory that a protein's location in a cell is important for its function - and have tested their method in yeast.
  • The work will help scientists determine what happens when individual proteins are pulled to a new location in a cell and forced to interact with other proteins they wouldn't normally come into contact with.
  • The work was funded by the Medical Research Council.