Biosynthesis of the Caenorhabditis elegans dauer pheromone
Biosynthesis of the Caenorhabditis elegans dauer pheromone
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DOI：
10.1073/pnas.0810338106
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发表时间：
2009-02-10
影响因子：
11.1
通讯作者：
Mak, Ho Yi
中科院分区：
文献类型：
--
作者：
Butcher, Rebecca A.;Ragains, Justin R.;Mak, Ho Yi
为了感知其种群密度并触发进入抗应激的dauer幼虫阶段，秀丽隐杆线虫使用dauer信息素，其由具有短的脂肪酸样侧链的蛔虫苷衍生物组成。虽然道尔信息素已经研究了25年，其生物合成是完全未知的。daf-22突变体是唯一已知的dauer信息素生产缺陷突变体。在这里，我们表明，daf-22编码的人类固醇载体蛋白SCPx，催化过氧化物酶体脂肪酸β-氧化的最后一步同源物。我们还表明，dhs-28，它编码的同源物的人类D-双功能蛋白，作用只是上游的SCPx，也是所需的信息素生产。长期培养的daf-22和dhs-28通过积累活性较低的长链脂肪酸蛔虫苷衍生物而产生dauer诱导活性。因此，daf-22和dhs-28是dauer信息素的短链脂肪酸衍生侧链的生物合成所必需的，并将dauer信息素的产生与代谢状态联系起来。
To sense its population density and to trigger entry into the stress-resistant dauer larval stage, Caenorhabditis elegans uses the dauer pheromone, which consists of ascaroside derivatives with short, fatty acid-like side chains. Although the dauer pheromone has been studied for 25 years, its biosynthesis is completely uncharacterized. The daf-22 mutant is the only known mutant defective in dauer pheromone production. Here, we show that daf-22 encodes a homolog of human sterol carrier protein SCPx, which catalyzes the final step in peroxisomal fatty acid beta-oxidation. We also show that dhs-28, which encodes a homolog of the human D-bifunctional protein that acts just upstream of SCPx, is also required for pheromone production. Long-term daf-22 and dhs-28 cultures develop dauer-inducing activity by accumulating less active, long-chain fatty acid ascaroside derivatives. Thus, daf-22 and dhs-28 are required for the biosynthesis of the short-chain fatty acid-derived side chains of the dauer pheromone and link dauer pheromone production to metabolic state.