Antagonistic Roles of Tau and MAP6 in Regulating Neuronal Development

Abstract Association of tau with microtubules causes them to be labile while association of MAP6 with microtubules causes them to be stable. As axons differentiate and grow long, tau and MAP6 segregate from one another on individual microtubules, resulting in the formation of stable and labile domains. The functional significance of the yin/yang relationship between tau and MAP6 remained speculative in those studies, with one idea being that such a relationship assists in balancing morphological stability with plasticity. Here, using primary rodent neuronal cultures, we show that depletion of tau has opposite effects compared to depletion of MAP6 on the rate of neuronal development, the efficiency of growth cone turning, and the number of processes and axonal branches. Opposite effects to those of tau depletion were also observed on the rate of neuronal migration, in an in vivo assay, when we depleted MAP6. When tau and MAP6 were depleted together in the cell culture assays, the morphological phenotypes negated one another. Tau and MAP6 are multifunctional proteins, but the present results suggest that the observed effects of their depletion on neuronal development are likely due to their opposite roles in regulating microtubule dynamics. Summary Tau and MAP6 play antagonistic roles in regulating multiple aspects of neuronal development, presumably via their antagonistic effects on microtubule dynamics.