GENE INACTIVATION OF PF11-1 OF PLASMODIUM-FALCIPARUM BY CHROMOSOME BREAKAGE AND HEALING - IDENTIFICATION OF A GAMETOCYTE-SPECIFIC PROTEIN WITH A POTENTIAL ROLE IN GAMETOGENESIS

被引:82
作者
SCHERF, A
CARTER, R
PETERSEN, C
ALANO, P
NELSON, R
AIKAWA, M
MATTEI, D
DASILVA, LP
LEECH, J
机构
[1] UNIV EDINBURGH,DEPT GENET,EDINBURGH EH9 3JN,MIDLOTHIAN,SCOTLAND
[2] SAN FRANCISCO GEN HOSP,SAN FRANCISCO,CA 94110
[3] UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143
[4] IST SUPER SANITA,CELL BIOL LAB,I-00161 ROME,ITALY
[5] CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106
关键词
CHROMOSOME BREAKAGE AND HEALING; GAMETOGENESIS; GENE DELETION; MALARIA; PF11-1; GENE;
D O I
10.1002/j.1460-2075.1992.tb05288.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We report the identification of the product of the Plasmodium falciparum Pf11-1 gene and demonstrate that it is a gametocyte-specific protein that has a potential role in the rupture of the host erythrocyte and emergence of the gametes (gametogenesis). The Pf11-1 gene is a large locus (30 kb) whose sequence predicts a glutamic acid-rich polypeptide. Our identification of the Pf11-1 gene product as gametocyte specific was greatly facilitated by the isolation of a mutant parasite clone in which > 90% of the Pf11-1 gene was deleted. Molecular analysis of the mutant locus suggests that the underlying genetic mechanism is chromosome breakage and subsequent healing by the addition of telomere repeats. PCR-based analysis showed that similar DNA rearrangements occur commonly in small subpopulations of most laboratory strains, suggesting that the Pf11-1 locus represents a fragile chromosome region. Northern blot analysis demonstrates that a large Pf11-1 gene-specific transcript (> > 10 kb) is present in gametocytes but not in asexual blood stage parasites. The Pf11-1 protein was localized by electron microscopy to granules in the cytoplasm of gametocytes adjacent to the membrane of the parasitophorous vacuole. Following in vitro stimulation of gametogenesis, the Pf11-1 protein was found in the membrane of lysed erythrocytes, suggesting a role for Pf11-1 in erythrocyte rupture within the mosquito gut.
引用
收藏
页码:2293 / 2301
页数:9
相关论文
共 29 条
[1]   STRUCTURE AND FUNCTION OF TELOMERES [J].
BLACKBURN, EH .
NATURE, 1991, 350 (6319) :569-573
[2]   EXPRESSION OF THE RESA GENE IN PLASMODIUM-FALCIPARUM ISOLATE FCR3 IS PREVENTED BY A SUBTELOMERIC DELETION [J].
CAPPAI, R ;
VANSCHRAVENDIJK, MR ;
ANDERS, RF ;
PETERSON, MG ;
THOMAS, LM ;
COWMAN, AF ;
KEMP, DJ .
MOLECULAR AND CELLULAR BIOLOGY, 1989, 9 (08) :3584-3587
[3]   PLASMODIUM-FALCIPARUM - AN ABUNDANT STAGE-SPECIFIC PROTEIN EXPRESSED DURING EARLY GAMETOCYTE DEVELOPMENT [J].
CARTER, R ;
GRAVES, PM ;
CREASEY, A ;
BYRNE, K ;
READ, D ;
ALANO, P ;
FENTON, B .
EXPERIMENTAL PARASITOLOGY, 1989, 69 (02) :140-149
[4]   PROPERTIES OF EPITOPES OF PFS 48/45, A TARGET OF TRANSMISSION BLOCKING MONOCLONAL-ANTIBODIES, ON GAMETES OF DIFFERENT ISOLATES OF PLASMODIUM-FALCIPARUM [J].
CARTER, R ;
GRAVES, PM ;
KEISTER, DB ;
QUAKYI, IA .
PARASITE IMMUNOLOGY, 1990, 12 (06) :587-603
[5]  
Carter R, 1988, MALARIA PRINCIPLES P, P253
[6]   SUPERCOIL SEQUENCING - A FAST AND SIMPLE METHOD FOR SEQUENCING PLASMID DNA [J].
CHEN, EY ;
SEEBURG, PH .
DNA-A JOURNAL OF MOLECULAR & CELLULAR BIOLOGY, 1985, 4 (02) :165-170
[7]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[8]   SEPARATION OF LARGE DNA-MOLECULES BY CONTOUR-CLAMPED HOMOGENEOUS ELECTRIC-FIELDS [J].
CHU, G ;
VOLLRATH, D ;
DAVIS, RW .
SCIENCE, 1986, 234 (4783) :1582-1585
[9]   REVERSAL OF KNOB FORMATION ON PLASMODIUM-FALCIPARUM INFECTED ERYTHROCYTES [J].
GRITZMACHER, CA ;
REESE, RT .
SCIENCE, 1984, 226 (4670) :65-67
[10]   THE POLYMORPHIC 11.1 LOCUS OF PLASMODIUM-FALCIPARUM [J].
KAHANE, B ;
SIBILLI, L ;
SCHERF, A ;
JAUREGUIBERRY, G ;
LANGSLEY, G ;
OZAKI, LS ;
GUILLOTTE, M ;
MULLERHILL, B ;
DASILVA, LP ;
MERCEREAUPUIJALON, O .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1987, 26 (1-2) :77-85