A CHROMOSOMAL REARRANGEMENT IN A PLASMODIUM-FALCIPARUM HISTIDINE-RICH PROTEIN GENE IS ASSOCIATED WITH THE KNOBLESS PHENOTYPE
A CHROMOSOMAL REARRANGEMENT IN A PLASMODIUM-FALCIPARUM HISTIDINE-RICH PROTEIN GENE IS ASSOCIATED WITH THE KNOBLESS PHENOTYPE
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DOI：
10.1038/322474a0
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发表时间：
1986-07-31
期刊：
影响因子：
64.8
通讯作者：
RAVETCH, JV
中科院分区：
文献类型：
--
作者：
POLOGE, LG;RAVETCH, JV
与恶性疟原虫相关的显着发病率和死亡率部分是由于毛细血管后微静脉中寄生红细胞的隔离所致，这可能会保护寄生虫免受脾脏清除1,2并导致脑型疟疾的发病机制3。这种隔离与感染红细胞表面寄生虫诱导的旋钮结构的表达有关，从而介导细胞粘附现象4,5。虽然旋钮对于细胞粘附是必要的，但它们还不够，需要寄生虫和宿主编码的蛋白质6-10。 P的自发突变体。恶性疟原虫已从体外培养物中分离出来，该培养物缺乏表达旋钮的能力并且无法细胞粘附11。一种富含组氨酸的蛋白质已被描述，它与旋钮表型 12 相关，并且可能是旋钮 13 的组成部分。我们现在报道了旋钮相关富含组氨酸蛋白 (KAHRP) 的互补 DNA 克隆的分离，并证明在无旋钮突变体中，该蛋白质的基因发生了重排，导致 3' 编码序列缺失。此外，KAHRP 基因映射的染色体在这些突变体中重新排列，产生截短基因的端粒位置。这些观察结果解释了此类突变体中信使 RNA 和蛋白质表达的丧失，并可能解释了旋钮本身的丧失。讨论了这种新机制对寄生虫中自发突变产生的影响。
The significant morbidity and mortality associated withPlasmodium falciparummalaria results, in part, from the sequestration of parasitized erythrocytes in postcapillary venules, which may protect the parasite from splenic clearance1,2and contribute to the pathogenesis of cerebral malaria3. This sequestration has been linked to the expression of parasite-induced knob structures on the surfacé of the infected erythrocyte which mediate the cyto-adherence phenomenon4,5. While knobs are necessary for cyto-adherence, they are not sufficient, requiring both parasite- and host-encoded proteins6–10. Spontaneous mutants ofP. falciparumhave been isolated fromin vitrocultures which lack the ability to express knobs and fail to cytoadhere11. A histidine-rich protein has been described which is associated with the knobby phenotype12and may be a constituent of the knob13. We now report the isolation of complementary DNA clones for a knob-associated histidine-rich protein (KAHRP) and demonstrate that in knobless mutants the gene for this protein has undergone a rearrangement, resulting in a deletion in the 3′ coding sequence. Moreover, the chromosome to which the KAHRP gene maps is rearranged in these mutants, producing a telomeric location of the truncated gene. These observations expláin the loss of expression of the, messenger RNA and protein in such mutants and may explain the loss of the knob itself. The implications for the generation of spontaneous mutations in the parasite by this novel mechanism are discussed.