Function of region I and II adhesive motifs of Plasmodium falciparum circumsporozoite protein in sporozoite motility and infectivity

Function of region I and II adhesive motifs of Plasmodium falciparum circumsporozoite protein in sporozoite motility and infectivity
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DOI:
10.1074/jbc.m208453200
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发表时间:
2002-12-06
影响因子:
4.8
通讯作者:
Crisanti, A
Crisanti, A
中科院分区:
生物学2区
文献类型:
--
作者:
Tewari, R;Spaccapelo, R;Crisanti, A

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恶性疟原虫环孢子子蛋白包含两个保守基序(I区和II区),它们分别在孢子子侵入涎腺和肝细胞的过程中与蚊子和脊椎动物宿主分子相互作用。为了研究该蛋白的功能,我们将伯氏疟原虫内源性环孢子子蛋白基因替换为恶性疟原虫的环孢子子蛋白基因,并替换为缺乏I区或II区的版本。我们发现恶性疟原虫环孢子子蛋白在啮齿动物寄生虫中起作用,携带恶性疟原虫CS基因的伯氏疟原虫孢子子发育正常,具有运动能力,侵入蚊子唾液腺,感染脊椎动物宿主。i区缺陷子孢子在载体和脊椎动物宿主中均未表现出运动性和传染性的损害。II区的破坏破坏了孢子子的运动能力,并极大地削弱了它们入侵蚊子唾液腺和感染脊椎动物宿主的能力。这些数据揭示了CS蛋白在孢子运动和感染性中的作用。
The circumsporozoite protein of Plasmodium falciparum contains two conserved motifs (regions I and II) that have been proposed to interact with mosquito and vertebrate host molecules in the process of sporozoite invasion of salivary glands and hepatocytes, respectively. To study the function of this protein we have replaced the endogenous circumsporozoite protein gene of Plasmodium berghei with that of P. falciparum and with versions lacking either region I or region II. We show here that P. falciparum circumsporozoite protein functions in rodent parasite and that P. berghei sporozoites carrying the P. falciparum CS gene develop normally, are motile, invade mosquito salivary glands, and infect the vertebrate host. Region I-deficient sporozoites showed no impairment of motility or infectivity in either vector or vertebrate host. Disruption of region II abolished sporozoite motility and dramatically impaired their ability to invade mosquito salivary glands and infect the vertebrate host. These data shed new light on the role of the CS protein in sporozoite motility and infectivity.