Rocking on Pins

Mitotic spindle positioning involves a conformational switch in LGN, the mammalian version of the invertebrate Pins protein, according to Quansheng Du and Ian Macara (University of Virginia, Charlottesville, VA). Interference with the switch induces a spindle rocking that represents the first genetically manipulable model for studying spindle positioning in vertebrates.

The switch operates via the opening of LGN, which can normally fold back onto itself. The unfolding is triggered by binding to either membrane-bound Gαi or NuMA, a protein that localizes to and stabilizes spindle poles. Unfolding was detected both as lack of self-binding and a mitotic reduction in FRET between fluorophores placed on either end of LGN.

In the cell, binding of NuMA to LGN appears to be a prerequisite for further interactions, as in cells lacking NuMA the LGN never made it...