ArticlemBio2015
Two Essential Light Chains Regulate the MyoA Lever Arm To Promote Toxoplasma Gliding Motility.
Article in mBio, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Identification of UCB-9721 as a potent inhibitor of MyoA, the essential class XIV myosin motor of apicomplexan parasites.bioRxiv : the preprint server for biology · 2026Article
- Protein arginine methyltransferase 5 is essential for virulence in Toxoplasma gondii.Parasites & vectors · 2026Article
- Bumped Kinase Inhibitor BKI-1708 Interferes in Cytokinesis and Drives Baryzoite Conversion in the Cyst-Forming Apicomplexan ParasitesInternational journal of molecular sciences · 2026Article
- The Centrocone Protein SMC_N1 Is Important for the Proliferation ofAnimals : an open access journal from MDPI · 2026Article
- Evolutionarily convergent mechanism of formin regulation coordinates actin polymerization in apicomplexan parasites.Science advances · 2025Article
- Immunization with the NcMYR1 gene knockout strain effectively protected C57BL/6 mice and their pups against theVirulence · 2024Article
- Myosin A and F-Actin play a critical role in mitochondrial dynamics and inheritance in Toxoplasma gondii.PLoS pathogens · 2024Article
- Myosin A and F-Actin play a critical role in mitochondrial dynamics and inheritance inbioRxiv : the preprint server for biology · 2024Article
- Construction of luciferase-expressing Neospora caninum and drug screening.Parasites & vectors · 2024Article
- MyosinA is a druggable target in the widespread protozoan parasite Toxoplasma gondii.PLoS biology · 2023Article
- A positive feedback loop mediates crosstalk between calcium, cyclic nucleotide and lipid signalling in calcium-induced Toxoplasma gondii egress.PLoS pathogens · 2022Article
- A Role for Basigin in Toxoplasma gondii Infection.Infection and immunity · 2022Article
- Dominique Soldati-Favre: BringingFrontiers in cellular and infection microbiology · 2022Article
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- Structural role of essential light chains in the apicomplexan glideosome.Communications biology · 2020Article
- Full-lengtheLife · 2020Article
- The Myosin Family of Mechanoenzymes: From Mechanisms to Therapeutic Approaches.Annual review of biochemistry · 2020Review
- Glutaredoxin 1 Deficiency Leads to Microneme Protein-Mediated Growth Defects inFrontiers in microbiology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
unlabelledKey to the virulence of apicomplexan parasites is their ability to move through tissue and to invade and egress from host cells. Apicomplexan motility requires the activity of the glideosome, a multicomponent molecular motor composed of a type XIV myosin, MyoA. Here we identify a novel glideosome component, essential light chain 2 (ELC2), and functionally characterize the two essential light chains (ELC1 and ELC2) of MyoA in Toxoplasma. We show that these proteins are functionally redundant but are important for invasion, egress, and motility. Molecular simulations of the MyoA lever arm identify a role for Ca(2+) in promoting intermolecular contacts between the ELCs and the adjacent MLC1 light chain to stabilize this domain. Using point mutations predicted to ablate either the interaction with Ca(2+) or the interface between the two light chains, we demonstrate their contribution to the quality, displacement, and speed of gliding Toxoplasma parasites. Our work therefore delineates the importance of the MyoA lever arm and highlights a mechanism by which this domain could be stabilized in order to promote invasion, egress, and gliding motility in apicomplexan parasites. IMPORTANCE: Tissue dissemination and host cell invasion by apicomplexan parasites such as Toxoplasma are pivotal to their pathogenesis. Central to these processes is gliding motility, which is driven by an actomyosin motor, the MyoA glideosome. Others have demonstrated the importance of the MyoA glideosome for parasite motility and virulence in mice. Disruption of its function may therefore have therapeutic potential, and yet a deeper mechanistic understanding of how it works is required. Ca(2+)-dependent and -independent phosphorylation and the direct binding of Ca(2+) to the essential light chain have been implicated in the regulation of MyoA activity. Here we identify a second essential light chain of MyoA and demonstrate the importance of both to Toxoplasma motility. We also investigate the role of Ca(2+) and the MyoA regulatory site in parasite motility and identify a potential mechanism whereby binding of a divalent cation to the essential light chains could stabilize the myosin to allow productive movement.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.