Characterisation of the Acto-MyoA motor complex in Toxoplasma gondii

Egarter, Saskia M (2014) Characterisation of the Acto-MyoA motor complex in Toxoplasma gondii. PhD thesis, University of Glasgow.

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In apicomplexan parasites, the machinery required for gliding motility is located between the plasma membrane and the Inner Membrane Complex (IMC). This type of motility depends on the regulated polymerisation and depolymerisation of actin and a multi-subunit complex, known as the Myosin A motor complex. This complex consists of the myosin heavy chain A (MyoA), the myosin light chain 1 (MLC1), the essential light chain 1 (ELC1) and three gliding-associated proteins (GAP40, GAP45 and GAP50). Gliding motility is thought to be essential for host cell egress and linked to active, parasite driven penetration of the host cell. Many components of this complex are extensively studied using either the ddFKBP system or the tetracycline-inducible knockdown system (Tet-system). Strikingly, while depletion of myoA has no impact on IMC formation, overexpression of the tail domain of MyoA results in a severe IMC biogenesis phenotype. In order to investigate this issue, conditional knockout (KO) mutants of the interacting partners of MyoA-tail were generated using the conditional site-specific DiCre recombination system. Indeed, GAP40 and GAP50 were identified as being essential for parasite replication and having a crucial role during IMC biogenesis. This is the first evidence showing that components of the MyoA motor complex fulfil essential functions during IMC formation and thus are not exclusively important for gliding motility dependant processes.
Several components of the MyoA motor complex were characterised using the Tet-system and showed a complete block in gliding motility, but not in host cell invasion. While it is possible that leaky expression of the gene in the knockdown mutants is responsible for this uncoupling of gliding motility and invasion, it remains feasible that different mechanisms are involved in these two processes. In order to shed light on this issue, conditional KOs for the Acto-MyoA motor complex were generated in this study and their functions during gliding dependent processes thoroughly analysed. Intriguingly, while depletion of individual components of this complex caused a severe block in host cell egress, gliding motility and host cell penetration were decreased, but not blocked, demonstrating an important, but not essential role of the Acto-MyoA motor complex during these processes. Altogether, this study raises questions of our current view of what drives gliding motility and invasion and supports the argument for critical revision of the linear motor model.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Toxoplasma gondii, Apicomplexa,biogenesis of the inner membrane complex, Acto-MyoA motor complex, glideosome associated proteins Myosin, Actin, Invasion, gliding motility
Subjects: Q Science > Q Science (General)
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Parasitology
Supervisor's Name: Meissner, Prof Markus
Date of Award: 2014
Depositing User: Saskia M Egarter
Unique ID: glathesis:2014-5351
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 31 Jul 2014 09:02
Last Modified: 31 Jul 2014 09:04

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