TRAMM makes an unscheduled stop during mitosis

A membrane trafficking protein moonlights during mitosis, helping to direct the motor protein CENP-E to the kinetochores, Milev et al. show.

The TRAPP protein complex controls membrane trafficking events such as tethering of vesicles to the Golgi apparatus. Milev et al. were surprised to discover that cells lacking the TRAPP component TRAMM (also known as TrappC12) showed mitotic defects. Mitotic chromosomes remained bunched at the spindle poles instead of lining up along the cellular midsection.

Although TRAMM remains in the cytoplasm during interphase, the researchers found small amounts of it clinging to chromosomes during metaphase. In cells lacking TRAMM, the outer kinetochores were missing several proteins. The kinetochore levels of CENP-E, which helps strengthen the attachments between chromosomes and microtubules, showed the largest decline in these cells.

To confirm that TRAMM helps attract CENP-E to the kinetochores, the researchers broke the microtubule–chromosome attachments with nocodazole. This treatment usually spurs some kinetochore components, whose levels drop after microtubule attachment, to return to the structures. Yet little CENP-E came back to the kinetochores in cells lacking TRAMM.

Milev et al. determined that TRAMM is phosphorylated early in mitosis and dephosphorylated before interphase begins, suggesting that its phosphorylation status determines which job it performs. Membrane trafficking shuts down during mitosis, so TRAMM is free to pursue its alternative role. How the protein recruits CENP-E to the kinetochores is unclear. Its interaction with CENP-E appears to be short-lived, but it could team up with other proteins.