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^?gS^?^M^^3^ffi^^^Siffili^J idBWfie^iilioulplfe^^ .-'r WMIOU* yto&*~: =s?ifcu ^A. $?ima&~ jim^^i,-^M^mK >^&*b^, . MM ^i^l.%?--.m^&&?? ?s*?w &tg^#s^?m&K&KM^>~ ***&?*?. ^J '~ ^ . ??"""""""". ^.>~^^MW j^aiaiss^''fsdm&ff""""""""! <&ffiiiltmffi&?wt rM6at..mgi.iii-...i. ,..in it.n .n.n ,_ J

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI064616-04
Application #
7541812
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Rogers, Martin J
Project Start
2005-12-15
Project End
2010-11-30
Budget Start
2008-12-01
Budget End
2009-11-30
Support Year
4
Fiscal Year
2009
Total Cost
$323,656
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Chen, Allan L; Moon, Andy S; Bell, Hannah N et al. (2017) Novel insights into the composition and function of the Toxoplasma IMC sutures. Cell Microbiol 19:
Kim, Elliot W; Nadipuram, Santhosh M; Tetlow, Ashley L et al. (2016) The Rhoptry Pseudokinase ROP54 Modulates Toxoplasma gondii Virulence and Host GBP2 Loading. mSphere 1:
Nadipuram, Santhosh M; Kim, Elliot W; Vashisht, Ajay A et al. (2016) In Vivo Biotinylation of the Toxoplasma Parasitophorous Vacuole Reveals Novel Dense Granule Proteins Important for Parasite Growth and Pathogenesis. MBio 7:
Wang, Kevin; Peng, Eric D; Huang, Amy S et al. (2016) Identification of Novel O-Linked Glycosylated Toxoplasma Proteins by Vicia villosa Lectin Chromatography. PLoS One 11:e0150561
Rodriguez, Jose A; Xu, Rui; Chen, Chien-Chun et al. (2015) Three-dimensional coherent X-ray diffractive imaging of whole frozen-hydrated cells. IUCrJ 2:575-83
Chen, Allan L; Kim, Elliot W; Toh, Justin Y et al. (2015) Novel components of the Toxoplasma inner membrane complex revealed by BioID. MBio 6:e02357-14
Silmon de Monerri, Natalie C; Yakubu, Rama R; Chen, Allan L et al. (2015) The Ubiquitin Proteome of Toxoplasma gondii Reveals Roles for Protein Ubiquitination in Cell-Cycle Transitions. Cell Host Microbe 18:621-33
Gold, Daniel A; Kaplan, Aaron D; Lis, Agnieszka et al. (2015) The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of Small Molecules between the Host and the Parasitophorous Vacuole. Cell Host Microbe 17:642-52
Tonkin, Michelle L; Beck, Josh R; Bradley, Peter J et al. (2014) The inner membrane complex sub-compartment proteins critical for replication of the apicomplexan parasite Toxoplasma gondii adopt a pleckstrin homology fold. J Biol Chem 289:13962-73
Beck, Josh R; Chen, Allan L; Kim, Elliot W et al. (2014) RON5 is critical for organization and function of the Toxoplasma moving junction complex. PLoS Pathog 10:e1004025

Showing the most recent 10 out of 28 publications