Effects of mutating α-tubulin lysine 40 on sensory dendrite development.
Effects of mutating α-tubulin lysine 40 on sensory dendrite development.
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DOI：
10.1242/jcs.210203
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发表时间：
2017-12-15
影响因子：
4
通讯作者：
Wildonger J
中科院分区：
文献类型：
--
作者：
Jenkins BV;Saunders HAJ;Record HL;Johnson-Schlitz DM;Wildonger J
微管对神经元的结构和功能至关重要。轴突和树突状微管富含影响微管动力学、转运和微管相关蛋白的翻译后修饰。α-微管蛋白赖氨酸40（K40）的乙酰化是神经元微管的一种重要和保守的修饰。然而，微管乙酰化的细胞作用仍然存在争议。为了解决微管乙酰化如何影响神经元形态发生，我们使用一种新的果蝇品系在体内突变内源性α-微管蛋白，该果蝇品系有助于快速敲入设计者α Tub 84 B等位基因（果蝇中主要的α-微管蛋白编码基因）。利用我们的新菌株，我们发现微管乙酰化，以及多聚谷氨酰胺化和（去）酪氨酸化，对生存不是必需的。然而，我们发现感觉神经元树突分支的细化依赖于α-微管蛋白K40。K40的突变揭示了树突溶酶体运输、微管聚合和Futsch蛋白在树突中而不是在轴突中的分布的中度但显著的变化。我们的研究指出了α-微管蛋白K40和乙酰化在树突形态发生中未被重视的作用。虽然我们的结果与乙酰化调节神经元内微管功能的想法一致，但它们也表明α-微管蛋白K40可能存在乙酰化独立的需求。这篇文章有一个相关的第一人称采访的论文的第一作者。 神经元富含翻译后修饰的微管。果蝇内源性α-微管蛋白的靶向突变揭示了树突分支的精细化被乙酰化阻断突变改变。
Microtubules are essential for neuronal structure and function. Axonal and dendritic microtubules are enriched in post-translational modifications that impact microtubule dynamics, transport and microtubule-associated proteins. Acetylation of α-tubulin lysine 40 (K40) is a prominent and conserved modification of neuronal microtubules. However, the cellular role of microtubule acetylation remains controversial. To resolve how microtubule acetylation might affect neuronal morphogenesis, we mutated endogenous α-tubulin in vivo using a new Drosophila strain that facilitates the rapid knock-in of designer αTub84B alleles (the predominant α-tubulin-encoding gene in flies). Leveraging our new strain, we found that microtubule acetylation, as well as polyglutamylation and (de)tyrosination, is not essential for survival. However, we found that dendrite branch refinement in sensory neurons relies on α-tubulin K40. Mutagenesis of K40 reveals moderate yet significant changes in dendritic lysosome transport, microtubule polymerization and Futsch protein distribution in dendrites but not in axons. Our studies point to an unappreciated role for α-tubulin K40 and acetylation in dendrite morphogenesis. While our results are consistent with the idea that acetylation tunes microtubule function within neurons, they also suggest there may be an acetylation-independent requirement for α-tubulin K40. This article has an associated First Person interview with the first author of the paper. Neurons are enriched in post-translationally modified microtubules. Targeted mutagenesis of endogenous α-tubulin in flies reveals that dendrite branch refinement is altered by acetylation-blocking mutations.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
影响因子：
16.6
作者：
Chauhan S;Ahmed Z;Bradfute SB;Arko-Mensah J;Mandell MA;Won Choi S;Kimura T;Blanchet F;Waller A;Mudd MH;Jiang S;Sklar L;Timmins GS;Maphis N;Bhaskar K;Piguet V;Deretic V
通讯作者：
Deretic V
影响因子：
16.2
作者：
Horton, AC;Rácz, B;Ehlers, MD
通讯作者：
Ehlers, MD
微管蛋白代码：分子成分、读出机制和功能。
DOI：
10.1083/jcb.201406055
发表时间：
2014-08-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Janke C
通讯作者：
Janke C