Overexpression and altered nucleocytoplasmic distribution of Anopheles ovalbumin-like SRPN10 serpins in Plasmodium-infected midgut cells

被引:48
作者
Danielli, A
Barillas-Mury, C
Kumar, S
Kafatos, FC
Loukeris, TG
机构
[1] European Mol Biol Lab, D-69117 Heidelberg, Germany
[2] Univ Bologna, Dipartimento Biol Evoluzionist Sperimentale, I-40126 Bologna, Italy
[3] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA
[4] NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA
[5] Inst Mol Biol & Biotechnol, FORTH, GR-71110 Iraklion, Greece
关键词
D O I
10.1111/j.1462-5822.2004.00445.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The design of effective, vector-based malaria transmission blocking strategies relies on a thorough understanding of the molecular and cellular interactions that occur during the parasite sporogonic cycle in the mosquito. During Plasmodium berghei invasion, transcription from the SRPN10 locus, encoding four serine protease inhibitors of the ovalbumin family, is strongly induced in the mosquito midgut. Herein we demonstrate that intense induction as well as redistribution of SRPN10 occurs specifically in the parasite-invaded midgut epithelial cells. Quantitative analysis establishes that in response to epithelial invasion, SRPN10 translocates from the nucleus to the cytoplasm and this is followed by strong SRPN10 overexpression. The invaded cells exhibit signs of apoptosis, suggesting a link between this type of intracellular serpin and epithelial damage. The SRPN10 gene products constitute a novel, robust and cell-autonomous marker of midgut invasion by ookinetes. The SRPN10 dynamics at the subcellular level confirm and further elaborate the 'time bomb' model of P. berghei invasion in both Anopheles stephensi and Anopheles gambiae. In contrast, this syndrome of responses is not elicited by mutant P. berghei ookinetes lacking the major ookinete surface proteins, P28 and P25. Molecular markers with defined expression patterns, in combination with mutant parasite strains, will facilitate dissection of the molecular mechanisms underlying vector competence and development of effective transmission blocking strategies.
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收藏
页码:181 / 190
页数:10
相关论文
共 29 条
[1]   The genome sequence of Drosophila melanogaster [J].
Adams, MD ;
Celniker, SE ;
Holt, RA ;
Evans, CA ;
Gocayne, JD ;
Amanatides, PG ;
Scherer, SE ;
Li, PW ;
Hoskins, RA ;
Galle, RF ;
George, RA ;
Lewis, SE ;
Richards, S ;
Ashburner, M ;
Henderson, SN ;
Sutton, GG ;
Wortman, JR ;
Yandell, MD ;
Zhang, Q ;
Chen, LX ;
Brandon, RC ;
Rogers, YHC ;
Blazej, RG ;
Champe, M ;
Pfeiffer, BD ;
Wan, KH ;
Doyle, C ;
Baxter, EG ;
Helt, G ;
Nelson, CR ;
Miklos, GLG ;
Abril, JF ;
Agbayani, A ;
An, HJ ;
Andrews-Pfannkoch, C ;
Baldwin, D ;
Ballew, RM ;
Basu, A ;
Baxendale, J ;
Bayraktaroglu, L ;
Beasley, EM ;
Beeson, KY ;
Benos, PV ;
Berman, BP ;
Bhandari, D ;
Bolshakov, S ;
Borkova, D ;
Botchan, MR ;
Bouck, J ;
Brokstein, P .
SCIENCE, 2000, 287 (5461) :2185-2195
[2]   Metalloproteinase inhibitors: biological actions and therapeutic opportunities [J].
Baker, AH ;
Edwards, DR ;
Murphy, G .
JOURNAL OF CELL SCIENCE, 2002, 115 (19) :3719-3727
[3]   Nucleocytoplasmic distribution of the ovalbumin serpin PI-9 requires a nonconventional nuclear import pathway and the export factor Crm1 [J].
Bird, CH ;
Blink, EJ ;
Hirst, CE ;
Buzza, MS ;
Steele, PM ;
Sun, JR ;
Jans, SA ;
Bird, PI .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (16) :5396-5407
[4]   Handbook of organization studies [J].
Birdsall, DG .
JOURNAL OF ACADEMIC LIBRARIANSHIP, 1998, 24 (01) :89-90
[5]   Immunity-related genes and gene families in Anopheles gambiae [J].
Christophides, GK ;
Zdobnov, E ;
Barillas-Mury, C ;
Birney, E ;
Blandin, S ;
Blass, C ;
Brey, PT ;
Collins, FH ;
Danielli, A ;
Dimopoulos, G ;
Hetru, C ;
Hoa, NT ;
Hoffmann, JA ;
Kanzok, SM ;
Letunic, I ;
Levashina, EA ;
Loukeris, TG ;
Lycett, G ;
Meister, S ;
Michel, K ;
Moita, LF ;
Müller, HM ;
Osta, MA ;
Paskewitz, SM ;
Reichhart, JM ;
Rzhetsky, A ;
Troxler, L ;
Vernick, KD ;
Vlachou, D ;
Volz, J ;
von Mering, C ;
Xu, JN ;
Zheng, LB ;
Bork, P ;
Kafatos, FC .
SCIENCE, 2002, 298 (5591) :159-165
[6]   1ST FIELD TRIAL OF AN IMMUNORADIOMETRIC ASSAY FOR THE DETECTION OF MALARIA SPOROZOITES IN MOSQUITOS [J].
COLLINS, FH ;
ZAVALA, F ;
GRAVES, PM ;
COCHRANE, AH ;
GWADZ, RW ;
AKOH, J ;
NUSSENZWEIG, RS .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1984, 33 (04) :538-543
[7]   GENETIC SELECTION OF A PLASMODIUM-REFRACTORY STRAIN OF THE MALARIA VECTOR ANOPHELES-GAMBIAE [J].
COLLINS, FH ;
SAKAI, RK ;
VERNICK, KD ;
PASKEWITZ, S ;
SEELEY, DC ;
MILLER, LH ;
COLLINS, WE ;
CAMPBELL, CC ;
GWADZ, RW .
SCIENCE, 1986, 234 (4776) :607-610
[8]   Cloning and characterization of four Anopheles gambiae serpin isoforms, differentially induced in the midgut by Plasmodium berghei invasion [J].
Danielli, A ;
Kafatos, FC ;
Loukeris, TG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (06) :4184-4193
[9]   Molecular interactions between Anopheles stephensi midgut cells and Plasmodium berghei:: the time bomb theory of ookinete invasion of mosquitoes [J].
Han, YS ;
Thompson, J ;
Kafatos, FC ;
Barillas-Mury, C .
EMBO JOURNAL, 2000, 19 (22) :6030-6040
[10]   The genome sequence of the malaria mosquito Anopheles gambiae [J].
Holt, RA ;
Subramanian, GM ;
Halpern, A ;
Sutton, GG ;
Charlab, R ;
Nusskern, DR ;
Wincker, P ;
Clark, AG ;
Ribeiro, JMC ;
Wides, R ;
Salzberg, SL ;
Loftus, B ;
Yandell, M ;
Majoros, WH ;
Rusch, DB ;
Lai, ZW ;
Kraft, CL ;
Abril, JF ;
Anthouard, V ;
Arensburger, P ;
Atkinson, PW ;
Baden, H ;
de Berardinis, V ;
Baldwin, D ;
Benes, V ;
Biedler, J ;
Blass, C ;
Bolanos, R ;
Boscus, D ;
Barnstead, M ;
Cai, S ;
Center, A ;
Chatuverdi, K ;
Christophides, GK ;
Chrystal, MA ;
Clamp, M ;
Cravchik, A ;
Curwen, V ;
Dana, A ;
Delcher, A ;
Dew, I ;
Evans, CA ;
Flanigan, M ;
Grundschober-Freimoser, A ;
Friedli, L ;
Gu, ZP ;
Guan, P ;
Guigo, R ;
Hillenmeyer, ME ;
Hladun, SL .
SCIENCE, 2002, 298 (5591) :129-+