Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
MRC Toxicology Unit, Gleeson Building, Tennis Court Road, Cambridge CB2 1QR, UK.
J Cell Sci. 2024 May 1;137(9). doi: 10.1242/jcs.261534. Epub 2024 May 10.
Microtubules are nucleated by γ-tubulin ring complexes (γ-TuRCs) and are essential for neuronal development. Nevertheless, γ-TuRC depletion has been reported to perturb only higher-order branching in elaborated Drosophila larval class IV dendritic arborization (da) neurons. This relatively mild phenotype has been attributed to defects in microtubule nucleation from Golgi outposts, yet most Golgi outposts lack associated γ-TuRCs. By analyzing dendritic arbor regrowth in pupae, we show that γ-TuRCs are also required for the growth and branching of primary and secondary dendrites, as well as for higher-order branching. Moreover, we identify the augmin complex (hereafter augmin), which recruits γ-TuRCs to the sides of pre-existing microtubules, as being required predominantly for higher-order branching. Augmin strongly promotes the anterograde growth of microtubules in terminal dendrites and thus terminal dendrite stability. Consistent with a specific role in higher-order branching, we find that augmin is expressed less strongly and is largely dispensable in larval class I da neurons, which exhibit few higher-order dendrites. Thus, γ-TuRCs are essential for various aspects of complex dendritic arbor development, and they appear to function in higher-order branching via the augmin pathway, which promotes the elaboration of dendritic arbors to help define neuronal morphology.
微管由 γ-微管蛋白环复合物(γ-TuRCs)引发,对于神经元发育至关重要。然而,据报道,γ-TuRC 的耗竭仅会扰乱复杂的果蝇幼虫 IV 类树突分支(da)神经元的高级分支。这种相对温和的表型归因于从高尔基末梢引发微管核的缺陷,但大多数高尔基末梢缺乏相关的 γ-TuRCs。通过分析蛹中的树突再生,我们表明 γ-TuRCs 对于初级和次级树突的生长和分支以及高级分支也很重要。此外,我们鉴定了 augmin 复合物(以下简称 augmin),它将 γ-TuRCs 招募到预先存在的微管的侧面,对于高级分支来说是必需的。augmin 强烈促进微管在末端树突中的正向生长,从而稳定末端树突。与在高级分支中的特定作用一致,我们发现 augmin 在幼虫 I 类 da 神经元中的表达较弱且在很大程度上是可有可无的,幼虫 I 类 da 神经元的高级树突很少。因此,γ-TuRCs 对于复杂树突发育的各个方面都是必不可少的,它们似乎通过 augmin 途径在高级分支中发挥作用,该途径促进树突的细化,有助于定义神经元形态。