Distribution and transport of cholesterol in Caenorhabditis elegans
Distribution and transport of cholesterol in Caenorhabditis elegans
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DOI：
10.1091/mbc.12.6.1725
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发表时间：
2001-06-01
影响因子：
3.3
通讯作者：
Kurzchalia, TV
中科院分区：
文献类型：
--
作者：
Matyash, V;Geier, C;Kurzchalia, TV
胆固醇转运是所有多细胞生物体的一个重要过程。在这项研究中，我们采用了两个最近开发的方法来调查的分布和分子机制的胆固醇运输秀丽隐杆线虫。胆固醇在活蠕虫中的分布是通过成像其荧光类似物脱氢麦角甾醇来研究的，我们通过喂食将其应用于动物。脱氢麦角固醇主要积累在L1-L3幼虫的咽部、神经环、排泄腺细胞和肠道中。随后，大量的脱氢麦角甾醇在卵母细胞和精子中积累。雄性显示出异常强烈的精子细胞标记，这表明胆固醇在精子发育中可能起作用。在一个补充的方法中，我们使用了一个光活化胆固醇类似物，以确定胆固醇结合蛋白在C。优雅的三个主要的和几个次要的蛋白质被发现专门交联后，紫外线照射的光胆固醇。主要蛋白质被鉴定为卵黄原蛋白。缺乏卵黄蛋白原受体的RME-2突变体不能在卵母细胞和胚胎中积累脱氢麦角甾醇，而是与卵黄蛋白原一起沿着在体腔中积累脱氢麦角甾醇。因此，C. elegans卵母细胞通过涉及卵黄蛋白的内吞途径发生。该途径可能是哺乳动物胆固醇转运的进化祖先。
Cholesterol transport is an essential process in all multicellular organisms. In this study we applied two recently developed approaches to investigate the distribution and molecular mechanisms of cholesterol transport in Caenorhabditis elegans. The distribution of cholesterol in living worms was studied by imaging its fluorescent analog, dehydroergosterol, which we applied to the animals by feeding. Dehydroergosterol accumulates primarily in the pharynx, nerve ring, excretory gland cell, and gut of L1-L3 larvae. Later, the bulk of dehydroergosterol accumulates in oocytes and spermatozoa. Males display exceptionally strong labeling of spermatids, which suggests a possible role for cholesterol in sperm development. In a complementary approach, we used a photoactivatable cholesterol analog to identify cholesterol-binding proteins in C. elegans. Three major and several minor proteins were found specifically cross-linked to photocholesterol after UV irradiation. The major proteins were identified as vitellogenins. rme-2 mutants, which lack the vitellogenin receptor, fail to accumulate dehydroergosterol in oocytes and embryos and instead accumulate dehydroergosterol in the body cavity along with vitellogenin. Thus, uptake of cholesterol by C. elegans oocytes occurs via an endocytotic pathway involving yolk proteins. The pathway is a likely evolutionary ancestor of mammalian cholesterol transport.