Antagonistic roles of tau and MAP6 in regulating neuronal development.

1. J Cell Sci. 2024 Oct 1;137(19):jcs261966. doi: 10.1242/jcs.261966. Epub 2024 Oct 7. Antagonistic roles of tau and MAP6 in regulating neuronal development. Sun X(1), Yu W(1), Baas PW(1), Toyooka K(1), Qiang L(1). Author information: (1)Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA. Association of tau (encoded by Mapt) with microtubules causes them to be labile, whereas association of MAP6 with microtubules causes them to be stable. As axons differentiate and grow, 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 remains speculative, with one idea being that such a relationship assists in balancing morphological stability with plasticity. Here, using primary rodent neuronal cultures, we show that tau depletion has opposite effects compared to MAP6 depletion on the rate of neuronal development, the efficiency of growth cone turning, and the number of neuronal processes and axonal branches. Opposite effects to those seen with tau depletion were also observed on the rate of neuronal migration, in an in vivo assay, when MAP6 was depleted. When tau and MAP6 were depleted together from neuronal cultures, the morphological phenotypes negated one another. Although tau and MAP6 are multifunctional proteins, our results suggest that the observed effects on neuronal development are likely due to their opposite roles in regulating microtubule stability. © 2024. Published by The Company of Biologists Ltd. DOI: 10.1242/jcs.261966 PMCID: PMC11491807 PMID: 39257379 [Indexed for MEDLINE] Conflict of interest statement: Competing interests The authors declare no competing or financial interests.