Role of actin filaments in the axonal transport of microtubules.
Microtubules originate at the centrosome of the neuron and are then released for transport down the axon, in which they can move both anterogradely and retrogradely during axonal growth. It has been hypothesized that these movements occur by force generation against the actin cytoskeleton. To test this, we analyzed the movement, distribution, and orientation of microtubules in neurons pharmacologically depleted of actin filaments. Actin depletion reduced but did not eliminate the anterograde movements and had no effect on the frequency of retrograde movements. Consistent with the idea that microtubules might also move against neighboring microtubules, actin depletion completely inhibited the outward transport of microtubules under experimental conditions of low microtubule density. Interestingly, visualization of microtubule assembly shows that actin depletion actually enhances the tendency of microtubules to align with one another. Such microtubule-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 that microtubules 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.
Hasaka
Thomas P
TP
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
Myers
Kenneth A
KA
Baas
Peter W
PW
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects / Q000502:physiology*; D001369:Axons / Q000502:physiology; D049108:Cell Enlargement; D016764:Cell Polarity; D002478:Cells, Cultured; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008870:Microtubules / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017783:Superior Cervical Ganglion / Q000166:cytology
D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins