Toxoplasma gondii targets a protein phosphatase 2C to the nuclei of a infected host cells

被引:120
作者
Gilbert, Luke A.
Ravindran, Sandeep
Turetzky, Jay M.
Boothroyd, John C.
Bradley, Peter J. [1 ]
机构
[1] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA
[2] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA
关键词
D O I
10.1128/EC.00309-06
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Intracellular pathogens have evolved a wide array of mechanisms to invade and co-opt their host cells for intracellular survival. Apicomplexan parasites such as Toxoplasma gondii employ the action of unique secretory organelles named rhoptries for internalization of the parasite and formation of a specialized niche within the host cell. We demonstrate that Toxoplasma gondii also uses secretion from the rhoptries during invasion to deliver a parasite-derived protein phosphatase 2C (PP2C-hn) into the host cell and direct it to the host nucleus. Delivery to the host nucleus does not require completion of invasion, as evidenced by the fact that parasites blocked in the initial stages of invasion with cytochalasin D are able to target PP2C-hn to the host nucleus. We have disrupted the gene encoding PP2C-hn and shown that PP2C-hn-knockout parasites exhibit a mild growth defect that can be rescued by complementation with the wild-type gene. The delivery of parasite effector proteins via the rhoptries provides a novel mechanism for Toxoplasma to directly access the command center of its host cell during infection by the parasite.
引用
收藏
页码:73 / 83
页数:11
相关论文
共 48 条
[11]   Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 angstrom resolution [J].
Das, AK ;
Helps, NR ;
Cohen, PTW ;
Barford, D .
EMBO JOURNAL, 1996, 15 (24) :6798-6809
[12]   Actin dynamics is controlled by a casein kinase II and phosphatase 2C interplay on Toxoplasma gondii toxofilin [J].
Delorme, V ;
Cayla, X ;
Faure, G ;
Garcia, A ;
Tardieux, I .
MOLECULAR BIOLOGY OF THE CELL, 2003, 14 (05) :1900-1912
[13]   Insertional tagging, cloning, and expression of the Toxoplasma gondii hypoxanthine-xanthine-guanine phosphoribosyltransferase gene - Use as a selectable marker for stable transformation [J].
Donald, RGK ;
Carter, D ;
Ullman, B ;
Roos, DS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (24) :14010-14019
[14]   Prediction of potential GPI-modification sites in proprotein sequences [J].
Eisenhaber, B ;
Bork, P ;
Eisenhaber, F .
JOURNAL OF MOLECULAR BIOLOGY, 1999, 292 (03) :741-758
[15]   Toxoplasma evacuoles:: a two-step process of secretion and fusion forms the parasitophorous vacuole [J].
Håkansson, S ;
Charron, AJ ;
Sibley, LD .
EMBO JOURNAL, 2001, 20 (12) :3132-3144
[16]  
Hill Dolores E., 2005, Animal Health Research Reviews, V6, P41, DOI 10.1079/AHR2005100
[17]   A host-targeting signal in virulence proteins reveals a secretome in malarial infection [J].
Hiller, NL ;
Bhattacharjee, S ;
van Ooij, C ;
Liolios, K ;
Harrison, T ;
Lopez-Estraño, C ;
Haldar, K .
SCIENCE, 2004, 306 (5703) :1934-1937
[18]  
Hooper NM, 2001, PROTEOMICS, V1, P748, DOI 10.1002/1615-9861(200106)1:6<748::AID-PROT748>3.3.CO
[19]  
2-K
[20]   Core of the partner switching signalling mechanism is conserved in the obligate intracellular pathogen Chlamydia trachomatis [J].
Hua, L ;
Hefty, PS ;
Lee, YJ ;
Lee, YM ;
Stephens, RS ;
Price, CW .
MOLECULAR MICROBIOLOGY, 2006, 59 (02) :623-636