Mask, the Drosophila Ankyrin Repeat and KH domain-containing protein, regulates microtubule dynamics

Published: March 29, 2021, 1:03 a.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.22.056051v1?rss=1 Authors: Zhu, M., Martinez, D. A., Guidry, J. J., Majeste, N., Mao, H., Yanofsky, S., Tian, X., Wu, C. Abstract: Proper regulation of microtubule (MT) dynamics is vital for essential cellular processes and many neuronal activities, including axonal transport and synaptic growth and remodeling. Here we demonstrate that Mask negatively regulates MT stability and maintains a balanced MT length and architecture in both fly larval muscles and motor neurons. In larval muscles, loss of mask increases MT length, and altering mask genetically modifies the Tau-induced MT fragmentation. In motor neurons, loss of mask function reduces the number of End-Binding Protein 1 (EB1)-positive MT plus-ends in the axons and results in overexpansion of the presynaptic terminal at larval neuromuscular junctions (NMJ). mask shows strong genetic interaction with stathmin (stai), a neuronal modulator of MT dynamics, in regulation of axon transportation and synaptic terminal stability. The structure/function analysis on Mask suggests that Mask's action in regulating MT stability does not depend on the nucleotide-binding function of its KH domain. Furthermore, through a proteomic approach, we found that Mask physically interacts with Jupiter, an MT stabilizing factor. The MT localization of Jupiter in the axons inversely correlates with Mask levels, suggesting that Mask may modulate MT stability by inhibiting the association of Jupiter to MTs. Copy rights belong to original authors. Visit the link for more info