The Tubulin Superfamily in Apicomplexan Parasites

Abstract

Microtubules and specialized microtubule-containing structures are assembled from tubulins, an ancient superfamily of essential eukaryotic proteins. Here, we use bioinformatic approaches to analyze features of tubulins in organisms from the phylum Apicomplexa. Apicomplexans are protozoan parasites that cause a variety of human and animal infectious diseases. Individual species harbor one to four genes each for α- and β-tubulin isotypes. These may specify highly similar proteins, suggesting functional redundancy, or exhibit key differences, consistent with specialized roles. Some, but not all apicomplexans harbor genes for δ- and ε-tubulins, which are found in organisms that construct appendage-containing basal bodies. Critical roles for apicomplexan δ- and ε-tubulin are likely to be limited to microgametes, consistent with a restricted requirement for flagella in a single developmental stage. Sequence divergence or the loss of δ- and ε-tubulin genes in other apicomplexans appears to be associated with diminished requirements for centrioles, basal bodies, and axonemes. Finally, because spindle microtubules and flagellar structures have been proposed as targets for anti-parasitic therapies and transmission-blocking strategies, we discuss these ideas in the context of tubulin-based structures and tubulin superfamily properties.

Properties and predicted functions of large genes and proteins of apicomplexan parasites

“…Notably, B. duncani ’s large proteins showed an overrepresentation of functions related to nuclear export and aminoacylation, Babesia microti ’s large proteins were characterized by a higher representation of functions associated with protein ubiquitination, whereas P. falciparum ’s large proteins displayed unique and parasite-specific annotations, with a highly significant presence of host cell binding functions ( P = 3.21e−39) compared to the rest of the proteome. In the case of P. vivax , unique functions enriched in its large proteins included cysteine peptidases and gamma-tubulin binding proteins, suggesting potential involvement in processes such as protein degradation, amino acid utilization, protein secretion, cytoskeletal organization ( 17 ) or nucleation of microtubule heterodimers ( 18 ) . Toxoplasma gondii ’s large proteome exhibited an overrepresentation of phosphodiesterase, chitin binding and zinc binding annotations.…”

Balancing Act: Tubulin Glutamylation and Microtubule Dynamics in Toxoplasma gondii

“…The T. gondii genome harbors genes for three α-tubulin isotypes (α1—TGME49_316400, α2—TGME49_231770, and α3—TGME49_231400) and three β-tubulin isotypes (β1—TGME49_266960, β2—TGME49_221620, and β3—TGME49_212240) [ 77 , 78 , 79 ]. According to a genome-wide CRISPR screen, α1-, α2-, β1-, and β2-tubulins are essential for in vitro tachyzoites, whereas α3- and β3-tubulins are not [ 80 ].…”

“…Some of these distinct features may be linked to specialized tubulin structures, such as the conoid and the flagellar axoneme [ 78 ]. Similar to other eukaryotes, the most divergent region in the amino acid sequences of the different T. gondii tubulin isotypes is localized at their C-terminal ends [ 77 , 79 ]. This region becomes exposed on the outer surface of MTs when tubulin dimers polymerize [ 81 ], providing binding sites for several MAPs and molecular motors [ 82 ].…”

p25alpha Domain-Containing Proteins of Apicomplexans and Related Taxa

“…Section 5.2 and Section 5.3 ). The purpose of this article is not to provide a detailed overview of apicomplexan cytoskeleton; previous and more recent excellent reviews have done so [ 48 , 49 , 50 ].…”