Function of the Caenorhabditis elegans ABC transporter PGP-2 in the biogenesis of a lysosome-related fat storage organelle
Function of the Caenorhabditis elegans ABC transporter PGP-2 in the biogenesis of a lysosome-related fat storage organelle
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DOI：
10.1091/mbc.e06-08-0685
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发表时间：
2007-03-01
影响因子：
3.3
通讯作者：
Hermann, Greg J.
中科院分区：
文献类型：
--
作者：
Schroeder, Lena K.;Kremer, Susan;Hermann, Greg J.
秀丽隐杆线虫肠道颗粒是肠道特异性的溶酶体相关细胞器，具有双折射和自发荧光。我们确定了pgp-2，它编码的ABC转运蛋白，在屏幕上的基因所需的肠道颗粒的正确形成。pgp-2（-）胚胎将双折射物质错误定位到肠腔中，并且缺乏酸化的含肠V-ATP酶的隔室。没有pgp-2（+）功能的成年人同样缺乏具有肠道颗粒特征的细胞器。这些细胞表型表明pgp-2（-）动物在肠道颗粒生物合成方面存在缺陷。双突变体分析表明，pgp-2（+）的功能与AP-3衔接复合物在肠道颗粒形成平行。我们发现，PGP-2是在肠道中表达，它的功能在肠道颗粒生物合成和PGP-2定位到肠道颗粒膜。这些结果支持ABC转运蛋白在调节溶酶体生物合成中的直接作用。以前，pgp-2（+）活性已被证明是尼罗红染色的脂肪在C.优雅的。我们表明，肠道颗粒的网站的脂肪储存在C。线虫胚胎和成虫。值得注意的是，在肠颗粒形成缺陷的动物中，甘油三酯水平相对正常。我们的结果为pgp-2（-）动物中尼罗红染色脂肪的损失提供了解释，并深入了解了这种与溶酶体相关的细胞器的特殊功能。
Caenorhabditis elegans gut granules are intestine specific lysosome-related organelles with birefringent and autofluorescent contents. We identified pgp-2, which encodes an ABC transporter, in screens for genes required for the proper formation of gut granules. pgp-2(-) embryos mislocalize birefringent material into the intestinal lumen and are lacking in acidified intestinal V-ATPase-containing compartments. Adults without pgp-2(+) function similarly lack organelles with gut granule characteristics. These cellular phenotypes indicate that pgp-2(-) animals are defective in gut granule biogenesis. Double mutant analysis suggests that pgp-2(+) functions in parallel with the AP-3 adaptor complex during gut granule formation. We find that pgp-2 is expressed in the intestine where it functions in gut granule biogenesis and that PGP-2 localizes to the gut granule membrane. These results support a direct role of an ABC transporter in regulating lysosome biogenesis. Previously, pgp-2(+) activity has been shown to be necessary for the accumulation of Nile Red-stained fat in C. elegans. We show that gut granules are sites of fat storage in C. elegans embryos and adults. Notably, levels of triacylglycerides are relatively normal in animals defective in the formation of gut granules. Our results provide an explanation for the loss of Nile Red-stained fat in pgp-2(-) animals as well as insight into the specialized function of this lysosome-related organelle.