Oocyte signals derived from polyunsaturated fatty acids control sperm recruitment in vivo
Oocyte signals derived from polyunsaturated fatty acids control sperm recruitment in vivo
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DOI：
10.1038/ncb1476
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发表时间：
2006-10-01
影响因子：
21.3
通讯作者：
Miller, Michael A.
中科院分区：
文献类型：
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作者：
Kubagawa, Homare M.;Watts, Jennifer L.;Miller, Michael A.
动物发育中的一个基本问题是运动细胞如何找到正确的目标。在秀丽隐杆线虫的交配过程中，雄性通过雌雄同体的外阴将精子注入子宫。变形虫精子在受精卵周围爬行到受精囊-受精发生的卷曲管（1，2）。在这里，我们表明，多不饱和脂肪酸（PUFAs），类花生酸信号分子的前体，在卵母细胞中的功能，以控制子宫内的精子运动方向。PUFA从脂肪代谢的位点肠转运到卵母细胞蛋黄，其是脂蛋白复合物。RME-2低密度脂蛋白（LDL）受体介导卵黄内吞作用（3）和脂肪酸转运到卵母细胞中，其缺失导致精子靶向功能严重缺陷。我们使用RNAi筛选来鉴定定向精子运动所需的脂质调节剂。我们的研究结果支持了这一假设，即PUFAs功能在卵母细胞作为前体的信号，控制精子募集到受精囊。PUFAs在哺乳动物和C.这些脂肪控制运动细胞向其靶组织的局部募集。
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(1,2). 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(3) 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.