A Plant-Like Kinase in Plasmodium falciparum Regulates Parasite Egress from Erythrocytes

被引:235
作者
Dvorin, Jeffrey D. [1 ,2 ]
Martyn, Derek C. [4 ]
Patel, Saurabh D. [1 ,3 ]
Grimley, Joshua S. [5 ]
Collins, Christine R. [6 ]
Hopp, Christine S. [7 ]
Bright, A. Taylor [8 ]
Westenberger, Scott [8 ]
Winzeler, Elizabeth [8 ,9 ]
Blackman, Michael J. [6 ]
Baker, David A. [7 ]
Wandless, Thomas J. [5 ]
Duraisingh, Manoj T. [1 ]
机构
[1] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA
[2] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA
[3] Childrens Hosp, Div Gastroenterol, Boston, MA 02115 USA
[4] Broad Inst, Cambridge, MA 02142 USA
[5] Stanford Univ, Dept Chem & Syst Biol, Stanford, CA 94305 USA
[6] Natl Inst Med Res, MRC, Div Parasitol, London NW7 1AA, England
[7] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England
[8] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
[9] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA
基金
美国国家卫生研究院; 英国惠康基金;
关键词
DEPENDENT PROTEIN-KINASE; MALARIA PARASITE; HOST-CELLS; TOXOPLASMA-GONDII; CALCIUM; EXPRESSION;
D O I
10.1126/science.1188191
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Clinical malaria is associated with the proliferation of Plasmodium parasites in human erythrocytes. The coordinated processes of parasite egress from and invasion into erythrocytes are rapid and tightly regulated. We have found that the plant-like calcium-dependent protein kinase PfCDPK5, which is expressed in invasive merozoite forms of Plasmodium falciparum, was critical for egress. Parasites deficient in PfCDPK5 arrested as mature schizonts with intact membranes, despite normal maturation of egress proteases and invasion ligands. Merozoites physically released from stalled schizonts were capable of invading new erythrocytes, separating the pathways of egress and invasion. The arrest was downstream of cyclic guanosine monophosphate-dependent protein kinase (PfPKG) function and independent of protease processing. Thus, PfCDPK5 plays an essential role during the blood stage of malaria replication.
引用
收藏
页码:910 / 912
页数:3
相关论文
共 22 条
[1]   Identification of proteases that regulate erythrocyte rupture by the malaria parasite Plasmodium falciparum [J].
Arastu-Kapur, Shirin ;
Ponder, Elizabeth L. ;
Fonovic, Ursa Pecar ;
Yeoh, Sharon ;
Yuan, Fang ;
Fonovic, Marko ;
Grainger, Munira ;
Phillips, Carolyn I. ;
Powers, James C. ;
Bogyo, Matthew .
NATURE CHEMICAL BIOLOGY, 2008, 4 (03) :203-213
[2]   An FKBP destabilization domain modulates protein levels in Plasmodium falciparum [J].
Armstrong, Christopher M. ;
Goldberg, Daniel E. .
NATURE METHODS, 2007, 4 (12) :1007-1009
[3]   A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules [J].
Banaszynski, Laura A. ;
Chen, Lin-chun ;
Maynard-Smith, Lystranne A. ;
Ooi, A. G. Lisa ;
Wandless, Thomas J. .
CELL, 2006, 126 (05) :995-1004
[4]   Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite [J].
Billker, O ;
Dechamps, S ;
Tewari, R ;
Wenig, G ;
Franke-Fayard, B ;
Brinkmann, V .
CELL, 2004, 117 (04) :503-514
[5]   Apicomplexan Parasites Co-Opt Host Calpains to Facilitate Their Escape from Infected Cells [J].
Chandramohanadas, Rajesh ;
Davis, Paul H. ;
Beiting, Daniel P. ;
Harbut, Michael B. ;
Darling, Claire ;
Velmourougane, Geetha ;
Lee, Ming Yeh ;
Greer, Peter A. ;
Roos, David S. ;
Greenbaum, Doron C. .
SCIENCE, 2009, 324 (5928) :794-797
[6]   Recent progress with FKBP-derived destabilizing domains [J].
Chu, Bernard W. ;
Banaszynski, Laura A. ;
Chen, Ling-chun ;
Wandless, Thomas J. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (22) :5941-5944
[7]   Heparan sulfate proteoglycans provide a signal to Plasmodium sporozoites to stop migrating and productively invade host cells [J].
Coppi, Alida ;
Tewari, Rita ;
Bishop, Joseph R. ;
Bennett, Brandy L. ;
Lawrence, Roger ;
Esko, Jeffrey D. ;
Billker, Oliver ;
Sinnis, Photini .
CELL HOST & MICROBE, 2007, 2 (05) :316-327
[8]   Molecular cloning and characterization of a second calcium-dependent protein kinase of Plasmodium falciparum [J].
Farber, PM ;
Graeser, R ;
Franklin, RM ;
Kappes, B .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1997, 87 (02) :211-216
[9]   The Motor Complex of Plasmodium falciparum PHOSPHORYLATION BY A CALCIUM-DEPENDENT PROTEIN KINASE [J].
Green, Judith L. ;
Rees-Channer, Roxanne R. ;
Howell, Stephen A. ;
Martin, Stephen R. ;
Knuepfer, Ellen ;
Taylor, Helen M. ;
Grainger, Munira ;
Holder, Anthony A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (45) :30980-30989
[10]   Plants, symbiosis and parasites: A calcium signalling connection [J].
Harper, JF ;
Harmon, A .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2005, 6 (07) :555-566