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The Role of Toxoplasma Rhoptries in Host Cell Infection

$323,656R01FY2009AINIH

University Of California Los Angeles, Los Angeles CA

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Abstract

Toxoplasma gondii is an obligate intracellularparasite in the phylumApicomplexa that causes severe central nervous system disorders of immunocompromised (AIDS/transplant/lymphoma)individualsand birth defects to congenitallyinfected neonates worldwide. This parasite also serves as a model system for the study of intracellular Apicomplexan parasites that cause a varitey of diseases of global medical andveterinary importance including Plasmodiumfalciparum, the causative agent of malaria. These parasites actively invade into and reside within a uniqueparasitophorous vacuole (PV) in the cytoplasm of the host. Invasionand establishment of the PV are mediated in part by the action of the rhoptries, secretory organelles uniqueto Apicomplexans. The precise role of the rhoptries in this process in not known, largely because only a few rhoptry proteins have been identified to date. To address the function of the rhoptries, we have purified rhoptries and analyzed their contents using proteomic and monoclonal antibody approaches. We have identified the major proteins constituents of the rhoptries, one of which is a protein phosphatase 2C-like (TgPP2L) protein that is targeted to the nucleus of the host cell during infection, indicatinga novel role for the rhoptries in host-parasite interaction. ^^SJi!i!Q^^^O^[unreadable]gS^[unreadable]^M^^3^ffi^^^Siffili^J idBWfie^iilioulplfe^^ .-'r WMIOU* yto&*~: =s[unreadable]ifcu ^A. $?ima&~ jim^^i,-^M^mK >^&*b^, . MM ^i^l.%[unreadable]--.m^&&[unreadable][unreadable] [unreadable]s*[unreadable]w &tg^#s^[unreadable]m&K&KM^>~ ***&[unreadable]*[unreadable]. ^J '~ ^ . [unreadable]?". ^<WT'^***'[unreadable]^iST^TV^^^!^TjTT^V^XiT^^ ^[unreadable]Wtm&*i'!^'Eii1HSMf^'[unreadable]"^^ I ^ST-OR" [unreadable]*[unreadable]%[unreadable]'[unreadable]"[unreadable][unreadable]a"*g|- '^.-"3$pv *q^- n*"*j"-: v^[unreadable]*wi[unreadable][unreadable] .T^BgiBr^te-dii-iBriSBii [unreadable]- -aanHJMifrfe. :sl.gBjC*5- Tsw^kw^i. rf*sa[unreadable]*- ~i[unreadable]OM^.*^. [unreadable]A<^U~->.>~^^MW j^aiaiss^''fsdm&ff"! <&ffiiiltmffi&[unreadable]w<?iKM8ifm[unreadable]>t rM6at..mgi.iii-...i. ,<a!fss^t^,i:.ft.Hn.Ti [unreadable][unreadable] [unreadable] ...,- [unreadable] n........._ni......:n-.iiapi* >..in it.n .n.n ,_ J

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