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Molecular dissection of gliding motility and host cell invasion by the apicomplexa

English title Molecular dissection of gliding motility and host cell invasion by the apicomplexa
Applicant Soldati-Favre Dominique
Number 116722
Funding scheme Project funding (Div. I-III)
Research institution Dépt Microbiologie et Médecine Moléculaire Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Biochemistry
Start/End 01.04.2007 - 31.03.2010
Approved amount 605'000.00
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All Disciplines (2)

Discipline
Biochemistry
Cellular Biology, Cytology

Keywords (6)

apicomplexa; parasite; toxoplasma gondii; plasmodium falciparum; plasmodium berghei; motility

Lay Summary (English)

Lead
Lay summary
Protozoan parasites belonging to the phylum of Apicomplexa are of enormous medical and veterinary significance, being responsible for a wide variety of diseases in human and animals, including malaria, toxoplasmosis, coccidiosis and cryptosporidiosis. Members of Apicomplexa are obligate intracellular parasites that have elaborated a unique and powerful mode of host cell entry. In the absence of locomotive organelles such as cilia or flagella, the invasive forms of these parasites exhibit an unusual form of substrate-dependent motility that is essential for host cell invasion and establishment of infection. Genetics studies have established that gliding motility and cell penetration by T. gondii needs intact parasite actin filaments (Dobrowolski and Sibley, 1996) and is powered by the action an essential class XIV myosin motor, which propels the parasite into host cells (Meissner et al., 2002b). Drugs that interfere with actin polymerization or stabilize actin filaments have profound effects on motility (Wetzel et al., 2003), yet the mechanism by which Apicomplexa control actin polymerization is unknown. Gliding is also associated with the discharge of several complexes of proteins (MICs) that are stored in the secretory organelles called micronemes. The MICs complexes are released on parasite surface upon a raise in parasite intracellular calcium level, they bind to host cell receptors and contribute critically to attachment, motility and invasion. Remarkably, most MICs are proteolytically cleaved during their biogenesis and/or post-exocytosis. Microneme protein protease 1 (MPP1) a rhomboid protease, is responsible for the intramembrane proteolytic cleavage leading to the release of the MICs from the parasite surface and indirect evidence suggest that this activity is essential for invasion in T. gondii (Brossier et al., 2003) and in P. falciparum (O'Donnell R et al., 2006). Despite some major progress a number of unresolved issues still persist: how is F-actin dynamics regulated? How many myosin motors contribute to the three forms of Toxoplasma motility during invasion? What is the molecular basis of T. gondii broad host range specificity? What is the mechanistic significance of microneme proteins shedding during invasion?Toxoplasma is an attractive model system due to its ease of experimental use, excellent tools for cellular and even biochemical studies, and well-developed genetic systems (Roos et al., 1994) and because the gliding mechanism is very conserved, the major findings hold true for other members of the Phylum including Plasmodium species responsible for malaria.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

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Associated projects

Number Title Start Funding scheme
131073 Study of factors governing the invasive and replicative modes in Apicomplexa 01.04.2010 Project funding (Div. I-III)
147118 Actomyosin-based motility and organelles biogenesis in Apicomplexans 01.04.2013 Project funding (Div. I-III)
102255 Dissection of gliding motility and host cell invasion by the apicomplexan parasites 01.01.2004 Project funding (Div. I-III)
147118 Actomyosin-based motility and organelles biogenesis in Apicomplexans 01.04.2013 Project funding (Div. I-III)

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