Proteome analysis of separated male and female gametocytes reveals novel sex-specific Plasmodium biology

Proteome analysis of separated male and female gametocytes reveals novel sex-specific Plasmodium biology
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DOI:
10.1016/j.cell.2005.03.027
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发表时间:
2005-06-03
期刊:
影响因子:
64.5
通讯作者:
Waters, AP
Waters, AP
中科院分区:
生物学1区
文献类型:
--
作者:
Khan, SM;Franke-Fayard, B;Waters, AP

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配子母细胞是疟疾寄生虫配子的前体细胞,在血液中循环,负责从宿主向蚊子媒介的传播。雄性和雌性配子体的个体蛋白质组使用质谱法进行分析,随后通过流式分选以性别特异性方式分离表达绿色荧光蛋白的转基因寄生虫。在转基因寄生虫启动子标签确认指定的阶段和性别特异性的蛋白质。雄性蛋白质组包含36%(650个中的236个)雄性特异性蛋白质,雌性蛋白质组包含19%(541个中的101个)雌性特异性蛋白质,但它们仅共享69个蛋白质,强调了性别的差异特征。在分析的所有疟疾生命周期阶段中,雄配子体具有最独特的蛋白质组,包含许多参与鞭毛运动和快速基因组复制的蛋白质。通过鉴定性别特异性蛋白激酶和磷酸酶,并使用两种激酶的靶向基因破坏,新的性别特异性调控途径被定义。
Gametocytes, the precursor cells of malaria-parasite gametes, circulate in the blood and are responsible for transmission from host to mosquito vector. The individual proteomes of male and female gametocytes were analyzed using mass spectrometry, following separation by flow sorting of transgenic parasites expressing green fluorescent protein, in a sex-specific manner. Promoter tagging in transgenic parasites confirmed the designation of stage and sex specificity of the proteins. The male proteome contained 36% (236 of 650) male-specific and the female proteome 19% (101 of 541) female-specific proteins, but they share only 69 proteins, emphasizing the diverged features of the sexes. Of all the malaria life-cycle stages analyzed, the male gametocyte has the most distinct proteome, containing many proteins involved in flagellar-based motility and rapid genome replication. By identification of gender-specific protein kinases and phosphatases and using targeted gene disruption of two kinases, new sex-specific regulatory pathways were defined.