Tubulin isotypes – functional insights from model organisms

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.

Genome-scale requirements for dynein-based trafficking revealed by a high-content arrayed CRISPR screen

“…However, 40 (11%) of the hits were associated with more subtle alterations in morphology of the microtubule network. These factors included genes encoding several tubulin isotypes 62 and TRiC/CCT components, as well as LIS1, the dynein light chain DYNLL1 and the dynactin component DCTN5. The observation of α-Tubulin phenotypes with crRNAs that target components of the dynein machinery is consistent with the motor's ability to modulate interphase microtubule networks [63][64][65] .…”

DYF-5/MAK–dependent phosphorylation promotes ciliary tubulin unloading

“…The role of multiple tubulin isotypes has been a major focus during the past decades but remains unresolved ( 23 ). The C. elegans tubulin family consists of nine α-, six β-, and one γ-tubulin, among which three α-tubulins, TBA-5, TBA-6, TBA-9, and one β-tubulin, TBB-4, localize in sensory cilia ( 24 , 25 ).…”

Microtubules in Microorganisms: How Tubulin Isotypes Contribute to Diverse Cytoskeletal Functions

“…Beyond these constraints, tubulin isotypes are able to coeveolve with distinct sets of regulatory proteins within organisms, and among various branches of evolution. Another key aspect that has become clear from work in microorganisms, as well as in other model systems ( Nsamba and Gupta, 2022 ), is that α- and β-tubulin tubulin isotypes are able to significantly influence the properties and function of cellular MTs when present at substochiometric levels within the polymer. This quality is critical for understanding how mutations in a single copy of various isotypes can underlie the range of observed tubulinopathies.…”

“…Another layer of regulation comes from a relatively large number of posttranslational modifications (PTMs) that occur on tubulin [reviewed in ( Janke and Magiera, 2020 )]. A third aspect of MT regulation stems from the multiple tubulin variants, or isotypes, expressed in most cells ( Figure 1 ) ( Nsamba and Gupta, 2022 ). Relative to our understanding of how PTMs and MAPs influence MT function, which can be significant, our knowledge of how tubulin isotypes themselves contribute to the complexity of MT behaviors remains limited.…”