Kubagawa Homare M, Watts Jennifer L, Corrigan Chad, Edmonds Johnathan W, Sztul Elizabeth, Browse John, Miller Michael A
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Nat Cell Biol. 2006 Oct;8(10):1143-8. doi: 10.1038/ncb1476. Epub 2006 Sep 24.
A fundamental question in animal development is how motile cells find their correct target destinations. During mating in the nematode Caenorhabditis elegans, males inject sperm through the hermaphrodite vulva into the uterus. Amoeboid sperm crawl around fertilized eggs to the spermatheca--a convoluted tube where fertilization occurs. Here, we show that polyunsaturated fatty acids (PUFAs), the precursors of eicosanoid signalling molecules, function in oocytes to control directional sperm motility within the uterus. PUFAs are transported from the intestine, the site of fat metabolism, to the oocytes yolk, which is a lipoprotein complex. Loss of the RME-2 low-density lipoprotein (LDL) receptor, which mediates yolk endocytosis and fatty acid transport into oocytes, causes severe defects in sperm targeting. We used an RNAi screen to identify lipid regulators required for directional sperm motility. Our results support the hypothesis that PUFAs function in oocytes as precursors of signals that control sperm recruitment to the spermatheca. A common property of PUFAs in mammals and C. elegans is that these fats control local recruitment of motile cells to their target tissues.
动物发育中的一个基本问题是运动细胞如何找到它们正确的目标目的地。在秀丽隐杆线虫交配过程中，雄性通过雌雄同体的阴门将精子注入子宫。变形虫状的精子围绕受精卵爬行至受精囊——一个发生受精的盘绕管道。在此，我们表明，类花生酸信号分子的前体多不饱和脂肪酸（PUFAs）在卵母细胞中发挥作用，以控制子宫内精子的定向运动。PUFAs从脂肪代谢部位肠道转运至卵母细胞的卵黄，卵黄是一种脂蛋白复合物。介导卵黄内吞作用和脂肪酸转运至卵母细胞的RME - 2低密度脂蛋白（LDL）受体缺失会导致精子靶向出现严重缺陷。我们使用RNA干扰筛选来鉴定精子定向运动所需的脂质调节因子。我们的结果支持这样一种假说，即PUFAs在卵母细胞中作为控制精子募集至受精囊的信号前体发挥作用。哺乳动物和秀丽隐杆线虫中PUFAs的一个共同特性是，这些脂肪控制运动细胞向其靶组织的局部募集。
