glo-3, a Novel Caenorhabditis elegans Gene, Is Required for Lysosome-Related Organelle Biogenesis
glo-3, a Novel Caenorhabditis elegans Gene, Is Required for Lysosome-Related Organelle Biogenesis
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DOI：
10.1534/genetics.108.093534
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发表时间：
2008-10-01
期刊：
影响因子：
3.3
通讯作者：
Hermann, Greg J.
中科院分区：
文献类型：
--
作者：
Rabbitts, Beverley M.;Ciotti, Marcela K.;Hermann, Greg J.
肠道颗粒是秀丽隐杆线虫肠道细胞中专门的溶酶体相关细胞器，作为脂肪储存的场所。我们确定了一个基因glo-3的突变，该基因在胚胎肠道颗粒的形成中起作用。一些glo-3（-）等位基因显示胚胎肠颗粒完全丧失，而另一些glo-3（-）等位基因的肠颗粒数量减少。glo-3等位基因的一个子集导致肠颗粒内容物错误定位到肠腔中，与细胞内运输缺陷一致。glo-3（-）胚胎缺乏消化道颗粒，发育成含有消化道颗粒的成体，表明. GLO-3（+）功能在发育过程中可能需要不同。我们发现，在肠道颗粒生物发生中，glo-3（+）与AP-3复合物和PGP-2 ABC转运蛋白平行或下游起作用。GLO-3编码预测的膜相关蛋白，其在线虫外缺乏明显的序列同源物。glo-3表达始于胚胎肠道前体细胞，并几乎完全持续存在于肠道细胞中直至成年。GLO-3：：GFP定位于肠颗粒膜，表明它可能在肠颗粒的运输事件中发挥直接作用。smg-1（-）对glo-3（-）无义等位基因的抑制表明，GLO-3的C-末端的一半（预计存在于细胞质中）对于肠颗粒的形成不是必需的。我们的研究将GLO-3确定为溶酶体相关细胞器形成的新参与者。
Gut granules are specialized lysosome-related organelles that act as sites of fat storage in Caenorhabditis elegans intestinal cells. We identified mutations in a gene, glo-3, that functions in the formation of embryonic gut granules. Some glo-3(-) alleles displayed a complete loss of embryonic gut granules, while other glo-3(-) alleles had reduced numbers of gut granules. A subset of glo-3 alleles led to mislocalization of gut granule contents into the intestinal lumen, consistent with a defect in intracellular trafficking. glo-3(-) embryos lacking gut granules developed into adults containing gut granules, indicating that. glo-3(+) function may be differentially required during development. We find that glo-3(+) acts in parallel with or downstream of the AP-3 complex and the PGP-2 ABC transporter in gut granule biogenesis. glo-3 encodes a predicted membrane-associated protein that lacks obvious sequence homologs out-side of nematodes. glo-3 expression initiates in embryonic intestinal precursors and persists almost exclusively in intestinal cells through adulthood. GLO-3:: GFP localizes to the gut granule membrane, suggesting it could play a direct role in the trafficking events at the gut granule. smg-1(-) Suppression of glo-3(-) nonsense alleles indicates that the C-terminal half of GLO-3, predicted to be present in the cytoplasm, is not necessary for gut granule formation. Our Studies identify GLO-3 as a novel player in the formation of lysosome-related organelles.