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Intracellular cargo transport: Molecular motors playing tug-of-war

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Intracellular transport is based on molecular motors that pull cargos along cytoskeletal filaments. Kinesin and dynein motors walk along microtubule filaments, while myosin motors move along actin filaments. One motor species walks actively only into one direction along the filament, e.g. kinesin-1 moves to the microtubule plus-end, whereas cytoplasmic dynein moves to the microtubule minus-end. However, many cellular cargos are observed to move bidirectionally, involving both plus- and minus-end-directed motors. The presumably simplest mechanism for such bidirectional transport is provided by a tug-of-war between the two motor species. We have studied this mechanism theoretically, using the load-dependent transport properties of individual motors as measured in single-molecule experiments. In contrast to previous expectations, such a tug-of-war is found to be highly cooperative and can lead to fast bidirectional motion with or without pauses, as observed in vivo. Our model reproduces experimental results on bidirectional transport of lipid droplets in Drosophila embryos, which have previously been thought to be incompatible with a tug-of-war scenario. One motor species walks actively only along one type of filament. However, the motor myosin-5, which walks actively along actin filaments, can passively diffuse along microtubules. Cargos that are transported along a microtubule by one kinesin and one myosin motor exhibit interspersed moving and diffusing events and increased processivity. We explain this behavior by a stochastic tug model similar to the tug-of-war model.

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