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

Abstract

The cellular functions of the microtubule (MT) cytoskeleton range from relatively simple to amazingly complex. Assembled from tubulin, a heterodimeric protein with α- and β-tubulin subunits, microtubules are long, hollow cylindrical filaments with inherent polarity. They are intrinsically dynamic polymers that utilize GTP binding by tubulin, and subsequent hydrolysis, to drive spontaneous assembly and disassembly. Early studies indicated that cellular MTs are composed of multiple variants, or isotypes, of α- and β-tubulins, and that these multi-isotype polymers are further diversified by a range of posttranslational modifications (PTMs) to tubulin. These findings support the multi-tubulin hypothesis whereby individual, or combinations of tubulin isotypes possess unique properties needed to support diverse MT structures and/or cellular processes. Beginning 40 years ago researchers have sought to address this hypothesis, and the role of tubulin isotypes, by exploiting experimentally accessible, genetically tractable and functionally conserved model systems. Among these systems, important insights have been gained from eukaryotic microbial models. In this review, we illustrate how using microorganisms yielded among the earliest evidence that tubulin isotypes harbor distinct properties, as well as recent insights as to how they facilitate specific cellular processes. Ongoing and future research in microorganisms will likely continue to reveal basic mechanisms for how tubulin isotypes facilitate MT functions, along with valuable perspectives on how they mediate the range of conserved and diverse processes observed across eukaryotic microbes.

The Tubulin Superfamily in Apicomplexan Parasites

“…Tubulins arose near to the appearance of the last common eukaryotic ancestor, and α-, β-, and γ- families are found in all eukaryotes [ 5 , 11 ]. Gene expansion within these families led to multiple genes for α-, β- and/or γ-tubulins, known as isoforms or isotypes [ 12 , 13 , 14 ]. Isotypes are typically distinguished by minor amino acid differences that modify biochemical properties to fine-tune temporal, structural, or cell-specific requirements [ 12 , 13 ].…”

“…Gene expansion within these families led to multiple genes for α-, β- and/or γ-tubulins, known as isoforms or isotypes [ 12 , 13 , 14 ]. Isotypes are typically distinguished by minor amino acid differences that modify biochemical properties to fine-tune temporal, structural, or cell-specific requirements [ 12 , 13 ]. Eukaryotes have one to two genes to specify γ-tubulins and may have from one to seven or more genes that encode α- and β- tubulin isotypes [ 15 , 16 , 17 ].…”

Model of the external force field for the protein folding process—the role of prefoldin

“…Prefoldin participates in the folding of the other protein, which is tubulin. Tubulin is a protein that is a major component of the eukaryote cytoskeleton ( Bera and Gupta, 2022 ). This group is represented in the present analysis by a single chain A (PDB ID—1FFX) ( Gigant et al, 2000 ) that is part of a complex termed the stathmin-like domain.…”

It takes tau to tango: Investigating the fuzzy interaction between the R2-repeat domain and tubulin C-terminal tails

“…All cells contain multiple variants (known as isotypes) of α and β-tubulin. While the sequence of the tubulin body is highly conserved, most of the sequence variation between isotypes is located on the CTTs, and it appears that these isotypes are not functionally interchangeable, 2, 3 as they might modulate the MT assembly, 4 dynamics 5 and interactions with other proteins. 6 In addition, tubulin CTTs are targets for many post-translational modifications (PTMs), and the diversity induced by these genetic and chemical variations is often referred to as the tubulin code , and acts as a fine regulator of microtubule function.…”