Liu Yanjie, Tewari Rita, Ning Jue, Blagborough Andrew M, Garbom Sara, Pei Jimin, Grishin Nick V, Steele Robert E, Sinden Robert E, Snell William J, Billker Oliver
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Genes Dev. 2008 Apr 15;22(8):1051-68. doi: 10.1101/gad.1656508. Epub 2008 Mar 26.
The cellular and molecular mechanisms that underlie species-specific membrane fusion between male and female gametes remain largely unknown. Here, by use of gene discovery methods in the green alga Chlamydomonas, gene disruption in the rodent malaria parasite Plasmodium berghei, and distinctive features of fertilization in both organisms, we report discovery of a mechanism that accounts for a conserved protein required for gamete fusion. A screen for fusion mutants in Chlamydomonas identified a homolog of HAP2, an Arabidopsis sterility gene. Moreover, HAP2 disruption in Plasmodium blocked fertilization and thereby mosquito transmission of malaria. HAP2 localizes at the fusion site of Chlamydomonas minus gametes, yet Chlamydomonas minus and Plasmodium hap2 male gametes retain the ability, using other, species-limited proteins, to form tight prefusion membrane attachments with their respective gamete partners. Membrane dye experiments show that HAP2 is essential for membrane merger. Thus, in two distantly related eukaryotes, species-limited proteins govern access to a conserved protein essential for membrane fusion.
雄雌配子间物种特异性膜融合背后的细胞和分子机制在很大程度上仍不清楚。在此，通过利用绿藻衣藻中的基因发现方法、啮齿动物疟原虫伯氏疟原虫中的基因破坏以及这两种生物体受精的独特特征，我们报告发现了一种机制，该机制解释了配子融合所需的一种保守蛋白。对衣藻中融合突变体的筛选鉴定出了拟南芥不育基因HAP2的一个同源物。此外，疟原虫中HAP2的破坏阻断了受精，从而阻断了疟疾的蚊子传播。HAP2定位于衣藻负配子的融合位点，但衣藻负配子和疟原虫hap2雄配子利用其他物种特异性蛋白，仍能够与各自的配子伴侣形成紧密的融合前膜附着。膜染料实验表明，HAP2对膜融合至关重要。因此，在两种远缘真核生物中，物种特异性蛋白控制着对膜融合所必需的一种保守蛋白的利用。
