The Ran GTPase orients the mitotic spindle by controlling the recruitment of a motor adaptor protein to the cell cortex, Wee et al. report.
Spindle orientation can determine the fate of daughter cells by affecting the proteins they inherit or the position they occupy within a tissue. A key factor controlling spindle alignment is the protein Pins, which localizes to the apical cortex and recruits both plus- and minus-end–directed microtubule motors to pull the spindle into position. Pins recruits the dynein–dynactin motor complex by binding to the adaptor protein Mud. It also recruits another protein required for spindle orientation, called Canoe, but Canoe's precise function in the process is unclear.
Wee et al. found that Canoe works with Pins to recruit Mud and orient the spindle. Cells lacking Canoe couldn't accurately align their spindles with a cortical patch of Pins because Mud was no longer recruited to the cortex. Although Canoe was found to directly bind to Pins, it doesn't appear to interact with Mud. Instead, the researchers found that Canoe promotes Mud's cortical recruitment by interacting with the GTP-bound form of Ran, a small GTPase that helps assemble the mitotic spindle. Cells expressing lower amounts of Ran, or a version of Canoe unable to bind the GTPase, couldn't recruit Mud to their cortical Pins domains and failed to orient their spindles correctly.
It remains to be seen how Ran and Canoe promote Mud's recruitment to the cell cortex. Wee et al. also want to identify additional proteins that help orient the spindle by performing an RNAi screen.