Alveolar proteins stabilize cortical microtubules in Toxoplasma gondii

Harding, C. R. , Gow, M., Kang, J. H., Shortt, E., Manalis, S. R., Meissner, M. and Lourido, S. (2019) Alveolar proteins stabilize cortical microtubules in Toxoplasma gondii. Nature Communications, 10, 401. (doi: 10.1038/s41467-019-08318-7) (PMID:30674885) (PMCID:PMC6344517)

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Single-celled protists use elaborate cytoskeletal structures, including arrays of microtubules at the cell periphery, to maintain polarity and rigidity. The obligate intracellular parasite Toxoplasma gondii has unusually stable cortical microtubules beneath the alveoli, a network of flattened membrane vesicles that subtends the plasmalemma. However, anchoring of microtubules along alveolar membranes is not understood. Here, we show that GAPM1a, an integral membrane protein of the alveoli, plays a role in maintaining microtubule stability. Degradation of GAPM1a causes cortical microtubule disorganisation and subsequent depolymerisation. These changes in the cytoskeleton lead to parasites becoming shorter and rounder, which is accompanied by a decrease in cellular volume. Extended GAPM1a depletion leads to severe defects in division, reminiscent of the effect of disrupting other alveolar proteins. We suggest that GAPM proteins link the cortical microtubules to the alveoli and are required to maintain the shape and rigidity of apicomplexan zoites.

Item Type:Articles
Additional Information:This study was supported by a Sir Henry Wellcome fellowship to CRH (103972/Z/14/Z), an ERC research grant (ERC2012-StG 309255-EndoTox) and Wellcome Senior fellowship (087582/Z/08/Z) to MM, an NIH Director’s Early Independence Award (1DP5OD017892) and an NIH Exploratory R21 grant (1R21AI123746) to SL, and by the Institute for Collaborative Biotechnologies through a grant (W911NF-09-0001) from the US Army Research Office to SRM.
Glasgow Author(s) Enlighten ID:Meissner, Professor Markus and Harding, Dr Clare and Gow, Mr Matthew
Authors: Harding, C. R., Gow, M., Kang, J. H., Shortt, E., Manalis, S. R., Meissner, M., and Lourido, S.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Nature Communications 10(1):401
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
659232Developing insights into Toxoplasma gondii pathogenesis through analysis of both parasite and host cell proteins required for the parasite's lifecycleClare HardingWellcome Trust (WELLCOTR)103972/Z/14/ZIII - PARASITOLOGY
501602Systematic analysis of essential parasite genes linked to invasion of the host cell in Toxoplasma gondiiMarkus MeissnerWellcome Trust (WELLCOTR)087582/Z/08/ZIII - PARASITOLOGY