Development/Plasticity/Repair Role of Actin Filaments in the Axonal Transport of

Microtubules originate at the centrosome of the neuron and are then released for transport down the axon, in which they canmove both anterogradely and retrogradely during axonal growth. It has been hypothesized that thesemovements occur by force generation against the actin cytoskeleton. To test this, we analyzed the movement, distribution, and orientation of microtubules in neurons pharmacolog-ically depleted of actin filaments. Actin depletion reduced but did not eliminate the anterograde movements and had no effect on the frequencyof retrogrademovements. Consistentwith the idea thatmicrotubulesmight alsomoveagainst neighboringmicrotubules, actin depletion completely inhibited the outward transport ofmicrotubules under experimental conditions of lowmicrotubule density. Inter-estingly, visualization of microtubule assembly shows that actin depletion actually enhances the tendency of microtubules to align with one another. Suchmicrotubule–microtubule interactions are sufficient to orient microtubules in their characteristic polarity pattern in axons grown overnight in the absence of actin filaments. In fact, microtubule behaviors were only chaotic after actin depletion in peripheral regions of the neuron in which microtubules are normally sparse and hence lack neighboring microtubules with which they could interact. On the basis of these results, we conclude thatmicrotubules are transported against either actin filaments or neighboring microtubules in the anterograde direction but only against other microtubules in the retrograde direction. Moreover, the transport of microtubules against one another provides a surprisingly effective option for the deployment and orientation of microtubules in the absence of actin filaments. Key words:microtubule; actin; neuron; axon; microtubule transport; microtubule assembl