Biochemistry Department, University of Wisconsin-Madison, Madison, WI 53706, USA.
Integrated Program in Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
J Cell Sci. 2017 Dec 15;130(24):4120-4131. doi: 10.1242/jcs.210203. Epub 2017 Nov 9.
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 using a new strain that facilitates the rapid knock-in of designer 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.
微管对于神经元的结构和功能至关重要。轴突和树突微管富含影响微管动力学、运输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突出且保守的修饰。然而，微管乙酰化的细胞作用仍存在争议。为了解微管乙酰化如何影响神经元形态发生，我们使用一种新的品系突变了内源性的α-微管，该品系便于快速敲入设计的等位基因（在果蝇中是主要的α-微管编码基因）。利用我们的新品系，我们发现微管乙酰化以及多聚谷氨酸化和（去）酪氨酸化对于生存并非必需。然而，我们发现感觉神经元的树突分支细化依赖于α-微管 K40。K40 的突变导致树突中的溶酶体运输、微管聚合和 Futsch 蛋白分布出现适度但显著的变化，但在轴突中没有。我们的研究表明，α-微管 K40 和乙酰化在树突形态发生中具有未被认识的作用。虽然我们的结果与乙酰化在神经元内调节微管功能的观点一致，但它们也表明可能存在对α-微管 K40 的乙酰化独立需求。本文有一篇与论文第一作者的第一人称访谈。
