Cell cycle-regulated tug-of-war between microtubule motors positions major trafficking organelles

Abstract

The morphology and integrity of the Golgi apparatus, which are critical for protein processing and sorting, undergo significant changes during interphase in proliferating mammalian cells. Initially compact during G1, the Golgi dissociates from the centrosomes in S-phase and transitions into an extended perinuclear ribbon in G2. The mechanisms underlying these changes remain unclear. Golgi positioning can be influenced by microtubule (MT)-dependent motors and membrane exchange with endoplasmic reticulum exit sites (ERES). We employ loss-of-function approaches and live-cell microscopy to demonstrate that CDK1-dependent signaling modulates the tug-of-war between plus- and minus-end-directed motors, resulting in differential positioning of the Golgi and ERES in G1 versus S/G2 phases. In G1, the Golgi and ERES are compacted by the minus-end-directed activity of dynein and KIFC3, respectively. In S/G2, organelle-specific combinations of kinesin-1 heavy and light chains overpower minus-end-directed motors. Our findings reveal a novel, cell cycle-regulated mechanism that coordinates organelle positioning via motor switching.