Self-organization mechanism of distinct microtubule orientations in axons and dendrites

Abstract

The identities of axons and dendrites are acquired through the self-organization of distinct microtubule (MT) orientations during neuronal polarization. The axon is generally characterized by a uniform MT orientation with all plus-ends pointing outward to the neurite terminal ('plus-end-out' pattern). On the other hand, the MT orientation pattern in the dendrites depends on species: vertebrate dendrites have a mixed alignment with both plus and minus ends facing either the terminal or the cell body ('mixed' pattern), whereas invertebrate dendrites have a 'minus-end-out' pattern. However, how MT organizations are developed in the axon and the dendrites is largely unknown. To investigate the mechanism of MT organization, we developed a biophysical model of MT kinetics, consisting of polymerization/depolymerization and MT catastrophe coupled with neurite outgrowth. The model simulation showed that the MT orientation can be controlled mainly by the speed of neurite growth and the hydrolysis rate. With a low hydrolysis rate, vertebrate plus-end-out and mixed microtubule patterns emerged in fast-and slow-growing neurites, respectively. In contrast, with a high hydrolysis rate, invertebrate plus-end-out and minus-end-out microtubule patterns emerged in fast-and slowgrowing neurites, respectively. Thus, our model can provide a unified understanding of distinct microtubule organizations by simply changing the parameters.