Structural and Functional Insights into the Microtubule Organizing Centers of Toxoplasma gondii and Plasmodium spp.

Abstract

Microtubule organizing centers (MTOCs) perform critical cellular tasks by nucleating, stabilizing, and anchoring microtubule’s minus ends. These capacities impact tremendously a wide array of cellular functions ranging from ascribing cell shape to orchestrating cell division and generating motile structures, among others. The phylum Apicomplexa comprises over 6000 single-celled obligate intracellular parasitic species. Many of the apicomplexan are well known pathogens such as Toxoplasma gondii and the Plasmodium species, causative agents of toxoplasmosis and malaria, respectively. Microtubule organization in these parasites is critical for organizing the cortical cytoskeleton, enabling host cell penetration and the positioning of large organelles, driving cell division and directing the formation of flagella in sexual life stages. Apicomplexans are a prime example of MTOC diversity displaying multiple functional and structural MTOCs combinations within a single species. This diversity can only be fully understood in light of each organism’s specific MT nucleation requirements and their evolutionary history. Insight into apicomplexan MTOCs had traditionally been limited to classical ultrastructural work by transmission electron microscopy. However, in the past few years, a large body of molecular insight has emerged. In this work we describe the latest insights into nuclear MTOC biology in two major human and animal disease causing Apicomplexans: Toxoplasma gondii and Plasmodium spp.

Separate To Operate: the Centriole-Free Inner Core of the Centrosome Regulates the Assembly of the Intranuclear Spindle in Toxoplasma gondii

“…These include, but are not limited to, CEP152, CEP57, CPAP (SAS-4), CEP192, pericentrin, CDK5RAP2 (Cnn), and a number of microtubule binding/stabilizing proteins, together with regulatory kinases and phosphatases (including Polo-like kinase 1, Aurora A kinase, and PP2 homologs). Strikingly, many of the functionally most important PCM proteins seem to be absent from the T. gondii genome ( 9 , 29 , 32 ). On the other hand, γ -tubulin, a crucial protein participating in spindle microtubule nucleation through the nucleation of the γ-tubulin ring complex (γTuRC) in other eukaryotes, has been previously localized to the outer core of the centrosome ( 9 , 33 ).…”

An Sfi1-like centrin-interacting centriolar plaque protein affects nuclear microtubule homeostasis

“…In mammals, centrosomes act as microtubule organizing centers (MTOC) and need to duplicate only once per cell cycle [27]. The CP of asexual blood stage parasites multiplies once each nuclear cycle and contains very few conserved centrosomal proteins [28][29][30]. The CP serves as a nucleation site for nuclear microtubules, while cytoplasmic microtubules are absent in schizonts [3,[31][32][33][34].…”

Paving the Way: Contributions of Big Data to Apicomplexan and Kinetoplastid Research

“…Stimulated emission depletion (STED) ( Willig et al., 2006 ), stochastic optical reconstruction microscopy (STORM) ( Rust et al., 2006 ), and structured illumination microscopy (SIM) ( Vangindertael et al., 2018 ) have all been used in the context of Kinetoplastid and Apicomplexan research. Expansion microscopy (ExM) ( Chen et al., 2015b ) and ultrastructure expansion microscopy (U-ExM) ( Gambarotto et al., 2021 ) have also been incorporated with great success ( Amodeo et al., 2021 ; Bertiaux et al., 2021 ; Dos Santos Pacheco and Soldati-Favre, 2021 ; Gorilak et al., 2021 ; Kalichava and Ochsenreiter, 2021 ; Liffner and Absalon, 2021 ; Tomasina et al., 2021 ). Despite their value, important bottlenecks for using super-resolution in a high-throughput manner are the time required for image acquisition, and the volume of data produced for quantitation.…”