In cell biology, the small mysteries are often the most difficult to solve. Decades of work on microtubules and the protein motors that drive them have revealed how they fit into everything from cell division to cell motility yet their place in the cell polarization puzzle has been missing. Now come ASCB members Urko del Castillo and Vladimir I. Gelfand and colleagues at the Feinberg School of Medicine at Northwestern with a piece of the missing puzzle. Writing in eLife, del Castillo and Gelfand say that polarization in early stage neurons in Drosophila is sorted out by microtubule sliding as the cells develop, first by the motor protein kinesin and then by the counter-directional motor, dynein.
This seems self-evident but it’s not. Microtubules are polar polymers, that is, they have a distinct plus end and a distinct minus end. Kinesin and dynein are one-way motors; kinesin is a plus-end motor so it drives microtubules with their minus ends out, while dynein pushes them with plus ends out and minus ends in. In maturing neurons, microtubule polarity is critical. The axon, the longest process of the neuron, has its microtubules plus-end out at the tips but the dendrites in flies have their microtubules the other way round (in mammalian neurons, microtubules in dendrites have mixed polarity). Yet early stage developing neurons in both flies and mammals have the polarity of their growing microtubules mixed every which way.
The Northwestern researchers now say that kinesin-1 initiates the neurite outgrowth by sliding anti-parallel microtubules (geometrically parallel but plus-minus opposites) apart, driving the neuron’s directional growth at the tip. As the axon elongates, dynein steps in to remove microtubules facing the “wrong” direction, using actin scaffolds to grip the cell membrane and push the minus-end microtubules toward the cell body. “The next challenge is to understand how dynein is attached to the actin scaffold and why it rearranges microtubules in axons, but not in dendrites,” say del Castillo and Gelfand.