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Vesicular roles of Arp2/3 nucleation-promoting factors
Dostál, Vojtěch ; Libusová, Lenka (advisor) ; Malínský, Jan (referee) ; Befekadu, Asfaw (referee)
F-actin is involved in key aspects of vesicular traffic, such as membrane deformation, tubulation and vesicle motion. Branching of F-actin is mediated by Arp2/3 but this complex must first be activated by so-called nucleation-promoting factors (NPFs). These factors play an essential role in the decision where and when branched actin should form on the membrane surface. The thesis focuses on the mechanisms which underlie localization and activation of NPFs, especially in terms of the phosphoinositide composition of the vesicle membranes. I show that one of the NPFs, the WASH complex, does not exclusively depend on the retromer complex for its membrane anchoring, as previously theorized. Rather, its understudied subunit SWIP enables the complex to independently bind to the membrane. I also present data showing that the WASH complex has essential roles in maintaining lysosomal function. Additionally, I elucidate the function of another NPF known as WHAMM in the ERGIC compartment, showing that it depends on the presence of myotubularin 9 for its ability to form membrane tubules. The thesis improves our understanding of the interface between the actin cytoskeleton and intracellular membrane system.
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How Intracellular Pathogens Manipulate Cellular Trafficking.
Petrů, Markéta ; Doležal, Pavel (advisor) ; Pyrih, Jan (referee)
Many intracellular single-celled organisms belong to medically important human pathogens. The selected parasites are subject of this thesis - Chlamydia spp., Legionella pneumophila, Trypanosoma cruzi and Toxoplasma gondii - as well as their interactions with the vesicular transport of the host cell. Basic pathways of vesicular transport are delineated and important participating molecules described. Furthermore, the effector proteins of pathogens that interact with these molecules are included. The special chapter is devoted to phenomenon of mimetics of SNARE proteins by bacteria. The manuscript concludes with a chapter on LpSNARE of Legionella pneumophila, which was found in our laboratory and which is a topic of my experimental work herein.
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How Intracellular Pathogens Manipulate Cellular Trafficking.
Petrů, Markéta ; Doležal, Pavel (advisor) ; Pyrih, Jan (referee)
Many intracellular single-celled organisms belong to medically important human pathogens. The selected parasites are subject of this thesis - Chlamydia spp., Legionella pneumophila, Trypanosoma cruzi and Toxoplasma gondii - as well as their interactions with the vesicular transport of the host cell. Basic pathways of vesicular transport are delineated and important participating molecules described. Furthermore, the effector proteins of pathogens that interact with these molecules are included. The special chapter is devoted to phenomenon of mimetics of SNARE proteins by bacteria. The manuscript concludes with a chapter on LpSNARE of Legionella pneumophila, which was found in our laboratory and which is a topic of my experimental work herein.
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