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Dynein (green) at the front of the cell helps the cell move.

Cytoplasmic dynein associates with a variety of intracellular cargos and pulls them toward the minus ends of microubules. But this retrograde motor protein is also essential for forward cell migration, as Dujardin et al. demonstrate on page 1205.

After observing dynein and its associated regulatory proteins at the leading edges of migrating cells in a monolayer model of wound healing, the authors inhibited dynein activity at various times to identify its functions. Early in cell migration, dynein helps reorganize the microtubule cytoskeleton, placing the centrosome on the leading edge side of the nucleus. Once this rearrangement is completed, inhibiting dynein does not change the location of the centrosome.

The motor protein is still required for cell migration even after cytoskeletal rearrangement. During migration, dynein appears in a diffuse area along the leading edge of the cell, where it seems to capture the plus ends of microtubules that enter the region. It is unclear whether dynein at the leading edge is activating lamellipodial protrusion or serving a strictly mechanical function, but the mechanism might have parallels with the action of dynein at the kinetochore, where it both pulls on microtubules and participates in mitotic checkpoint signaling. ▪