Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, U.K.
Essays Biochem. 2018 Dec 7;62(6):765-780. doi: 10.1042/EBC20180028.
In this short review, we give an overview of microtubule nucleation within cells. It is nearly 30 years since the discovery of γ-tubulin, a member of the tubulin superfamily essential for proper microtubule nucleation in all eukaryotes. γ-tubulin associates with other proteins to form multiprotein γ-tubulin ring complexes (γ-TuRCs) that template and catalyse the otherwise kinetically unfavourable assembly of microtubule filaments. These filaments can be dynamic or stable and they perform diverse functions, such as chromosome separation during mitosis and intracellular transport in neurons. The field has come a long way in understanding γ-TuRC biology but several important and unanswered questions remain, and we are still far from understanding the regulation of microtubule nucleation in a multicellular context. Here, we review the current literature on γ-TuRC assembly, recruitment, and activation and discuss the potential importance of γ-TuRC heterogeneity, the role of non-γ-TuRC proteins in microtubule nucleation, and whether γ-TuRCs could serve as good drug targets for cancer therapy.
在这篇简短的综述中，我们概述了细胞内微管的成核。自从发现 γ-微管蛋白以来，已经将近 30 年了，γ-微管蛋白是微管超家族的成员，对于所有真核生物中适当的微管成核是必不可少的。γ-微管蛋白与其他蛋白质结合形成多蛋白 γ-微管蛋白环复合物（γ-TuRC），模板并催化微管丝 OTHERWISE 动力学不利的组装。这些纤维可以是动态的或稳定的，它们执行多种功能，例如有丝分裂期间的染色体分离和神经元内的细胞内运输。该领域在理解 γ-TuRC 生物学方面已经取得了长足的进步，但仍有几个重要的未解决的问题，我们仍远未理解多细胞环境中微管成核的调控。在这里，我们回顾了关于 γ-TuRC 组装、招募和激活的当前文献，并讨论了 γ-TuRC 异质性的潜在重要性、非 γ-TuRC 蛋白在微管成核中的作用，以及 γ-TuRC 是否可以作为癌症治疗的良好药物靶点。
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