Egan et al. clarify the role of the dynein co-factor Lis1 in cargo transport.

The molecular motor dynein ferries cargoes toward the minus ends of microtubules, typically toward the nucleus. The role of Lis1 has been controversial. Although researchers agree that Lis1 helps dynein position nuclei and centrosomes within the cell, they disagree about whether Lis1 aids dynein in other situations and how it influences the motor protein. In particular, whether Lis1 continues to interact with dynein once the cargo has started rolling is uncertain.

Egan et al. took a closer look at Lis1’s actions by tracking the movement of fluorescently labeled cargoes in the long hyphae of the fungus Aspergillus nidulans. They found that Lis1 was essential for relocating not only nuclei, but also endosomes and peroxisomes. That Lis1 takes part in shipping such diverse cargoes raises the possibility that it participates in transportation of all dynein cargoes, the researchers say.

In fungi lacking Lis1, dynein failed to associate with endosomes and peroxisomes, which therefore mostly stalled and amassed at the tips of hyphae. But the team noticed that the few endosomes that got moving traveled at a normal pace, suggesting that Lis1’s role involves starting rather than sustaining movement. In normal cells, more than 90% of moving endosomes were attached to dynein, but less than 2% of them were associated with Lis1. The results support the notion that Lis1’s job entails loading cargo onto dynein rather than transporting it.

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J. Cell Biol.