Opposite-polarity motors activate one another to trigger cargo transport in live cells

TLDR

Intracellular transport is bidirectional and depends on kinesin‑1 and dynein cooperating; loss of either motor abolishes the other's cargo movement. The study investigates whether replacing endogenous kinesin‑1 or dynein with a peroxisome‑targeted motor of the same polarity can induce opposite‑direction peroxisome transport. Using Drosophila S2 cells, the authors substituted kinesin‑1 or dynein with peroxisome‑targeted motors and monitored peroxisome motility. Motility‑deficient motors that still bind microtubules and hydrolyze ATP do not activate peroxisome movement, showing that active movement is required; consequently, any pair of opposite‑polarity motors moving on microtubules can activate each other, demonstrating that mechanical interactions between opposite‑polarity motors are necessary and sufficient for bidirectional organelle transport in live cells.

Abstract

Intracellular transport is typically bidirectional, consisting of a series of back and forth movements. Kinesin-1 and cytoplasmic dynein require each other for bidirectional transport of intracellular cargo along microtubules; i.e., inhibition or depletion of kinesin-1 abolishes dynein-driven cargo transport and vice versa. Using Drosophila melanogaster S2 cells, we demonstrate that replacement of endogenous kinesin-1 or dynein with an unrelated, peroxisome-targeted motor of the same directionality activates peroxisome transport in the opposite direction. However, motility-deficient versions of motors, which retain the ability to bind microtubules and hydrolyze adenosine triphosphate, do not activate peroxisome motility. Thus, any pair of opposite-polarity motors, provided they move along microtubules, can activate one another. These results demonstrate that mechanical interactions between opposite-polarity motors are necessary and sufficient for bidirectional organelle transport in live cells.