Schistosoma mansoni Polo-like kinase 1: A mitotic kinase with key functions in parasite reproduction

被引:42
作者
Long, Thavy [1 ]
Cailliau, Katia [2 ]
Beckmann, Svenja [3 ]
Browaeys, Edith [2 ]
Trolet, Jacques [1 ]
Grevelding, Christoph G. [3 ]
Dissous, Colette [1 ]
机构
[1] Univ Lille Nord France, Inst Pasteur Lille, CNRS UMR 8204, CIIL,Inserm U1019, F-59019 Lille, France
[2] Univ Lille 1 Sci & Technol, Lab Regulat, Signaux Div, EA 4020,IFR 147, F-59655 Villeneuve Dascq, France
[3] Univ Giessen, Inst Parasitol, D-35392 Giessen, Germany
关键词
Schistosoma mansoni; Polo-like kinase; Reproduction; Kinase inhibitor; PROTEIN-KINASE; TYROSINE KINASE; STE20-LIKE KINASE; MOLECULAR-CLONING; CATALYTIC DOMAIN; BINDING DOMAIN; EGG-PRODUCTION; INHIBITOR; 3-KINASE; FAMILY;
D O I
10.1016/j.ijpara.2010.03.002
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
Polo-like kinases (Plks) are conserved regulators of mitosis. In mammals, Plk1 is over-expressed in a wide range of tumour cells and constitutes a valuable target for anti-cancer therapy. This work presents the characterisation of the Plk1 homologue (SmPlk1) of Schistosoma mansoni, a trematode responsible for schistosomiasis, one of the most important parasitic diseases, second only to malaria. The intense levels of disease transmission and the severity of pathologies are the consequences of the exceptional reproductive activity of schistosomes, in which Plks may play a decisive role. Structural and functional analyses of SmPlk1 have demonstrated its homology with other Plk1 members and its conserved function in mitotic processes. Activation of SmPlk1 was shown to be dependent on phosphorylation of its conserved threonine residue (T-182) and the ability of active SmPlk1 to induce mitosis was demonstrated in the Xenopus oocyte model. SmPlk1 transcripts were detected abundantly in parasite stages containing a high amount of germinal cells. A potential role of SmPlk1 in mitosis and/or meiosis in schistosomes was supported by the in situ detection of StriPlk1 transcripts in female vitelline cells and oocytes as well as in male spermatocytes. Several Plk inhibitors were shown to inhibit SmPlk1 activity in Xeno pus oocytes, and BI 2536 (the first-in-class prototype Plk1 inhibitor) induced in vitro dramatic alterations in schistosome gonads, which affected oogenesis and spermatogenesis. These results indicate a major role for SmPlk1 in parasite reproduction and suggest its importance as a potential new target against schistosomiasis. (C) 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1075 / 1086
页数:12
相关论文
共 64 条
[1]   Current chemotherapy arsenal for schistosomiasis mansoni: alternatives and challenges [J].
Abdul-Ghani, Rashad ;
Loutfy, Naguiba ;
El Sahn, Amel ;
Hassan, Azza .
PARASITOLOGY RESEARCH, 2009, 104 (05) :955-965
[2]   A New Family of Receptor Tyrosine Kinases with a Venus Flytrap Binding Domain in Insects and Other Invertebrates Activated by Aminoacids [J].
Ahier, Arnaud ;
Rondard, Philippe ;
Gouignard, Nadege ;
Khayath, Naji ;
Huang, Siluo ;
Trolet, Jacques ;
Donoghue, Daniel J. ;
Gauthier, Monique ;
Pin, Jean-Philippe ;
Dissous, Colette .
PLOS ONE, 2009, 4 (05)
[3]   The Drosophila orthologue of xPlkk1 is not essential for Polo activation and is necessary for proper contractile ring formation [J].
Alves, PS ;
Godinho, SA ;
Tavares, AA .
EXPERIMENTAL CELL RESEARCH, 2006, 312 (03) :308-321
[4]   Polo-like kinases: conservation and divergence in their functions and regulation [J].
Archambault, Vincent ;
Glover, David M. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (04) :265-275
[5]   Schistosoma mansoni: signal transduction processes during the development of the reproductive organs [J].
Beckmann, S. ;
Quack, T. ;
Burmeister, C. ;
Buro, C. ;
Long, T. ;
Dissous, C. ;
Grevelding, C. G. .
PARASITOLOGY, 2010, 137 (03) :497-520
[6]   The Syk Kinase SmTK4 of Schistosoma mansoni Is Involved in the Regulation of Spermatogenesis and Oogenesis [J].
Beckmann, Svenja ;
Buro, Christin ;
Dissous, Colette ;
Hirzmann, Joerg ;
Grevelding, Christoph G. .
PLOS PATHOGENS, 2010, 6 (02)
[7]   The genome of the blood fluke Schistosoma mansoni [J].
Berriman, Matthew ;
Haas, Brian J. ;
LoVerde, Philip T. ;
Wilson, R. Alan ;
Dillon, Gary P. ;
Cerqueira, Gustavo C. ;
Mashiyama, Susan T. ;
Al-Lazikani, Bissan ;
Andrade, Luiza F. ;
Ashton, Peter D. ;
Aslett, Martin A. ;
Bartholomeu, Daniella C. ;
Blandin, Gaelle ;
Caffrey, Conor R. ;
Coghlan, Avril ;
Coulson, Richard ;
Day, Tim A. ;
Delcher, Art ;
DeMarco, Ricardo ;
Djikeng, Appolinaire ;
Eyre, Tina ;
Gamble, John A. ;
Ghedin, Elodie ;
Gu, Yong ;
Hertz-Fowler, Christiane ;
Hirai, Hirohisha ;
Hirai, Yuriko ;
Houston, Robin ;
Ivens, Alasdair ;
Johnston, David A. ;
Lacerda, Daniela ;
Macedo, Camila D. ;
McVeigh, Paul ;
Ning, Zemin ;
Oliveira, Guilherme ;
Overington, John P. ;
Parkhill, Julian ;
Pertea, Mihaela ;
Pierce, Raymond J. ;
Protasio, Anna V. ;
Quail, Michael A. ;
Rajandream, Marie-Adele ;
Rogers, Jane ;
Sajid, Mohammed ;
Salzberg, Steven L. ;
Stanke, Mario ;
Tivey, Adrian R. ;
White, Owen ;
Williams, David L. ;
Wortman, Jennifer .
NATURE, 2009, 460 (7253) :352-U65
[8]   Signal transduction pathways triggered by fibroblast growth factor receptor 1 expressed in Xenopus laevis oocytes after fibroblast growth factor 1 addition -: Role of Grb2, phosphatidylinositol 3-kinase, Src tyrosine kinase, and phospholipase Cγ [J].
Browaeys-Poly, E ;
Cailliau, K ;
Vilain, JP .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2000, 267 (20) :6256-6263
[9]   Chemotherapy of schistosomiasis: present and future [J].
Caffrey, Conor R. .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2007, 11 (04) :433-439
[10]   KINETICS OF EGG-PRODUCTION AND EGG EXCRETION BY SCHISTOSOMA-MANSONI AND SCHISTOSOMA-JAPONICUM IN MICE INFECTED WITH A SINGLE PAIR OF WORMS [J].
CHEEVER, AW ;
MACEDONIA, JG ;
MOSIMANN, JE ;
CHEEVER, EA .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1994, 50 (03) :281-295