ABSTRACT 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.
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Tubulin mutations in brain development disorders: Why haploinsufficiency does not explain TUBA1A tubulinopathies
The neuronal cytoskeleton performs incredible feats during nervous system development. Extension of neuronal processes, migration, and synapse formation rely on the proper regulation of microtubules. Mutations that disrupt the primary α‐tubulin expressed during brain development,
- NSF-PAR ID:
- 10458077
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Cytoskeleton
- Volume:
- 77
- Issue:
- 3-4
- ISSN:
- 1949-3584
- Page Range / eLocation ID:
- p. 40-54
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Microtubules are dynamic cytoskeleton filaments that are essential for a wide range of cellular processes. They are polymerized from tubulin, a heterodimer of α- and β-subunits. Most eukaryotic organisms express multiple isotypes of α- and β-tubulin, yet their functional relevance in any organism remains largely obscure. The two α-tubulin isotypes in budding yeast, Tub1 and Tub3, are proposed to be functionally interchangeable, yet their individual functions have not been rigorously interrogated. Here, we develop otherwise isogenic yeast strains expressing single tubulin isotypes at levels comparable to total tubulin in WT cells. Using genome-wide screening, we uncover unique interactions between the isotypes and the two major mitotic spindle positioning mechanisms. We further exploit these cells to demonstrate that Tub1 and Tub3 optimize spindle positioning by differentially recruiting key components of the Dyn1- and Kar9-dependent mechanisms, respectively. Our results provide novel mechanistic insights into how tubulin isotypes allow highly conserved microtubules to function in diverse cellular processes.
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