Mask, the Drosophila ankyrin repeat and KH domain-containing protein, affects microtubule stability.
Mask, the Drosophila ankyrin repeat and KH domain-containing protein, affects microtubule stability.
复制标题
DOI：
10.1242/jcs.258512
复制
发表时间：
2021-10-15
影响因子：
4
通讯作者：
Wu C
中科院分区：
文献类型：
--
作者：
Martinez D;Zhu M;Guidry JJ;Majeste N;Mao H;Yanofsky ST;Tian X;Wu C
适当调节微管（MT）的稳定性和动力学对基本细胞过程至关重要，包括神经元轴突运输和突触生长和重塑。在本研究中，我们证明了果蝇锚蛋白重复序列和含KH结构域的蛋白面罩对幼虫肌肉和运动神经元的MT稳定性都有负面影响。在幼虫肌肉中，掩膜功能的丧失会增加MT聚合物的长度，在运动神经元中，掩膜功能的丧失会导致幼虫神经肌肉连接处（NMJs）的突触前末端过度扩张。在轴突运输和突触末端稳定性的调节中，蒙膜与stastmin （stai）基因相互作用。我们对Mask的结构-功能分析表明，其含有锚蛋白重复结构域的n端部分足以介导Mask对MT稳定性的影响。此外，我们发现Mask负调控运动神经元轴突中mt相关蛋白Jupiter的丰度，并且神经元敲除Jupiter部分抑制了NMJs幼虫的Mask功能丧失表型。综上所述，我们的研究表明Mask是一种新的MT稳定性调节器，而Mask的这种作用需要木星的正常功能。摘要：蒙膜是一种新的果蝇MT稳定性调节因子。Mask与MT的两个重要调节剂Tau和Stathmin （Stai）有显著的相互作用，这两个调节剂的突变与人类疾病有关。
Proper regulation of microtubule (MT) stability and dynamics is vital for essential cellular processes, including axonal transportation and synaptic growth and remodeling in neurons. In the present study, we demonstrate that the Drosophila ankyrin repeat and KH domain-containing protein Mask negatively affects MT stability in both larval muscles and motor neurons. In larval muscles, loss-of-function of mask increases MT polymer length, and in motor neurons, loss of mask function results in overexpansion of the presynaptic terminal at the larval neuromuscular junctions (NMJs). mask genetically interacts with stathmin (stai), a neuronal modulator of MT stability, in the regulation of axon transportation and synaptic terminal stability. Our structure–function analysis of Mask revealed that its ankyrin repeats domain-containing N-terminal portion is sufficient to mediate Mask's impact on MT stability. Furthermore, we discovered that Mask negatively regulates the abundance of the MT-associated protein Jupiter in motor neuron axons, and that neuronal knocking down of Jupiter partially suppresses mask loss-of-function phenotypes at the larval NMJs. Taken together, our studies demonstrate that Mask is a novel regulator for MT stability, and such a role of Mask requires normal function of Jupiter. Summary: Mask is a novel regulator of MT stability in Drosophila. Mask shows prominent interplay with two important modulators of MT, Tau and Stathmin (Stai), whose mutations are related to human diseases.
登录
查看更多内容
影响因子：
8.4
作者：
Dhyani, Anamika;Machado-Neto, Joao A.;Olalla Saad, Sara T.
通讯作者：
Olalla Saad, Sara T.
影响因子：
5.3
作者：
Franco, B;Bogdanik, L;Grau, Y
通讯作者：
Grau, Y
影响因子：
4.6
作者：
Chabu, Chiswili;Doe, Chris Q.
通讯作者：
Doe, Chris Q.
影响因子：
64.5
作者：
Blower, MD;Nachury, M;Weis, K
通讯作者：
Weis, K
影响因子：
7
作者：
Brooks AN;Duff MO;May G;Yang L;Bolisetty M;Landolin J;Wan K;Sandler J;Booth BW;Celniker SE;Graveley BR;Brenner SE
通讯作者：
Brenner SE