Publisher Correction: Cryo-EM structure of cortical microtubules from human parasite Toxoplasma gondii identifies their microtubule inner proteins

The organization of the microtubule cytoskeleton is dictated by microtubule nucleators or organizing centers. Toxoplasma gondii, an important human parasite, has an array of 22 regularly spaced cortical microtubules stemming from a hypothesized organizing center, the apical polar ring. Here we examine the functions of the apical polar ring by characterizing two of its components, KinesinA and APR1, and show that its putative role in templating can be separated from its mechanical stability. Parasites that lack both KinesinA and APR1 (ΔkinesinAΔapr1) are capable of generating 22 cortical microtubules. However, the apical polar ring is fragmented in live ΔkinesinAΔapr1 parasites and is undetectable by electron microscopy after detergent extraction. Disintegration of the apical polar ring results in the detachment of groups of microtubules from the apical end of the parasite. These structural defects are linked to a diminished ability of the parasite to move and invade host cells, as well as decreased secretion of effectors important for these processes. Together the findings demonstrate the importance of the structural integrity of the apical polar ring and the microtubule array in the Toxoplasma lytic cycle, which is responsible for massive tissue destruction in acute toxoplasmosis.

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An ensemble of specifically targeted proteins stabilizes cortical microtubules in the human parasite Toxoplasma gondii

Molecular Biology of the Cell ◽

10.1091/mbc.e15-11-0754 ◽

2016 ◽

Vol 27 (3) ◽

pp. 549-571 ◽

Cited By ~ 20

Author(s):

Jun Liu ◽

Yudou He ◽

Imaan Benmerzouga ◽

William J. Sullivan ◽

Naomi S. Morrissette ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Mitotic Spindle ◽

Functional Differentiation ◽

Cortical Microtubules ◽

Human Parasite ◽

Cellular Morphogenesis ◽

Associated Proteins ◽

Spindle Microtubules ◽

The Stability ◽

Directional Transport

Although all microtubules within a single cell are polymerized from virtually identical subunits, different microtubule populations carry out specialized and diverse functions, including directional transport, force generation, and cellular morphogenesis. Functional differentiation requires specific targeting of associated proteins to subsets or even subregions of these polymers. The cytoskeleton of Toxoplasma gondii, an important human parasite, contains at least five distinct tubulin-based structures. In this work, we define the differential localization of proteins along the cortical microtubules of T. gondii, established during daughter biogenesis and regulated by protein expression and exchange. These proteins distinguish cortical from mitotic spindle microtubules, even though the assembly of these subsets is contemporaneous during cell division. Finally, proteins associated with cortical microtubules collectively protect the stability of the polymers with a remarkable degree of functional redundancy.

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Stability and function of a putative microtubule organizing center in the human parasite Toxoplasma gondii

10.1101/099267 ◽

2017 ◽

Author(s):

Jacqueline M. Leung ◽

Yudou He ◽

Fangliang Zhang ◽

Yu-Chen Hwang ◽

Eiji Nagayasu ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Structural Integrity ◽

Lytic Cycle ◽

Host Cells ◽

Structural Defects ◽

Cortical Microtubules ◽

Microtubule Organizing Center ◽

Polar Ring ◽

Human Parasite ◽

Organizing Center

ABSTRACTThe organization of the microtubule cytoskeleton is dictated by microtubule nucleators or organizing centers. Toxoplasma gondii, an important human parasite, has an array of 22 regularly spaced cortical microtubules stemming from a hypothesized organizing center, the apical polar ring. Here, we examine the functions of the apical polar ring by characterizing two of its components, KinesinA and APR1, and discovered that its putative role in templating can be separated from its mechanical stability. Parasites that lack both KinesinA and APR1 (ΔkinesinAΔapr1) are capable of generating 22 cortical microtubules. However, the apical polar ring is fragmented in live ΔkinesinAΔapr1 parasites, and is undetectable by electron microscopy after detergent extraction. Disintegration of the apical polar ring results in the detachment of groups of microtubules from the apical end of the parasite. These structural defects are linked to a diminished ability of the parasite to move and to invade host cells, as well as decreased secretion of effectors important for these processes. Together, the findings demonstrate the importance of the structural integrity of the apical polar ring and the microtubule array in the Toxoplasma lytic cycle, which is responsible for massive tissue destruction in acute toxoplasmosis.

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Cryo-EM structure of cortical microtubules from human parasite Toxoplasma gondii identifies their microtubule inner proteins

Nature Communications ◽

10.1038/s41467-021-23351-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Xiangli Wang ◽

Yong Fu ◽

Wandy L. Beatty ◽

Meisheng Ma ◽

Alan Brown ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Ex Vivo ◽

Structural Basis ◽

Cortical Microtubules ◽

Human Pathogen ◽

Chemical Treatments ◽

Human Parasite ◽

Evolutionarily Conserved ◽

Bona Fide ◽

The Stability

AbstractIn living cells, microtubules (MTs) play pleiotropic roles, which require very different mechanical properties. Unlike the dynamic MTs found in the cytoplasm of metazoan cells, the specialized cortical MTs from Toxoplasma gondii, a prevalent human pathogen, are extraordinarily stable and resistant to detergent and cold treatments. Using single-particle cryo-EM, we determine their ex vivo structure and identify three proteins (TrxL1, TrxL2 and SPM1) as bona fide microtubule inner proteins (MIPs). These three MIPs form a mesh on the luminal surface and simultaneously stabilize the tubulin lattice in both longitudinal and lateral directions. Consistent with previous observations, deletion of the identified MIPs compromises MT stability and integrity under challenges by chemical treatments. We also visualize a small molecule like density at the Taxol-binding site of β-tubulin. Our results provide the structural basis to understand the stability of cortical MTs and suggest an evolutionarily conserved mechanism of MT stabilization from the inside.

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