Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA.
J Cell Sci. 2022 May 1;135(9). doi: 10.1242/jcs.259539. Epub 2022 May 6.
The microtubule cytoskeleton is assembled from the α- and β-tubulin subunits of the canonical tubulin heterodimer, which polymerizes into microtubules, and a small number of other family members, such as γ-tubulin, with specialized functions. Overall, microtubule function involves the collective action of multiple α- and β-tubulin isotypes. However, despite 40 years of awareness that most eukaryotes harbor multiple tubulin isotypes, their role in the microtubule cytoskeleton has remained relatively unclear. Various model organisms offer specific advantages for gaining insight into the role of tubulin isotypes. Whereas simple unicellular organisms such as yeast provide experimental tractability that can facilitate deeper access to mechanistic details, more complex organisms, such as the fruit fly, nematode and mouse, can be used to discern potential specialized functions of tissue- and structure-specific isotypes. Here, we review the role of α- and β-tubulin isotypes in microtubule function and in associated tubulinopathies with an emphasis on the advances gained using model organisms. Overall, we argue that studying tubulin isotypes in a range of organisms can reveal the fundamental mechanisms by which they mediate microtubule function. It will also provide valuable perspectives on how these mechanisms underlie the functional and biological diversity of the cytoskeleton.
微管细胞骨架由典型的微管二聚体的α-和β-微管蛋白亚基组装而成,微管二聚体聚合形成微管,还有少数其他家族成员,如γ-微管蛋白,具有特殊功能。总的来说,微管的功能涉及多种α-和β-微管蛋白同工型的集体作用。然而,尽管人们已经意识到大多数真核生物都含有多种微管蛋白同工型,但它们在微管细胞骨架中的作用仍然相对不清楚。各种模式生物为深入了解微管蛋白同工型的作用提供了具体的优势。虽然像酵母这样的简单单细胞生物提供了实验的可操作性,可以更深入地了解机制细节,但更复杂的生物,如果蝇、线虫和老鼠,可以用来识别组织和结构特异性同工型的潜在特殊功能。在这里,我们回顾了α-和β-微管蛋白同工型在微管功能和相关微管病中的作用,重点介绍了使用模式生物所取得的进展。总的来说,我们认为在一系列生物体中研究微管蛋白同工型可以揭示它们介导微管功能的基本机制。它还将为这些机制如何为细胞骨架的功能和生物学多样性提供有价值的视角。