Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic
Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic
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DOI：
10.1038/ncb1627
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发表时间：
2007-09-01
影响因子：
21.3
通讯作者：
Grant, Barth D.
中科院分区：
文献类型：
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作者：
Balklava, Zita;Pant, Saumya;Grant, Barth D.
在全基因组RNA介导的干扰筛选膜交通所需的基因，包括内吞摄取，再循环从内体到质膜，和分泌，我们确定了168个候选内吞调节剂和100个候选分泌调节剂。这些候选人中的许多是高度保守的后生动物，但以前没有牵连在这些过程中。在筛选的阳性细胞中，我们鉴定了PAR-3、PAR-6、PKC-3和CDC-42，这些蛋白质在胚胎和上皮细胞极性产生中的重要性是众所周知的。进一步的分析表明，内吞运输秀丽隐杆线虫体腔细胞和人HeLa细胞也受到损害后，扰动CDC-42/Cdc 42或PAR-6/Par 6功能，表明这些蛋白质在调节内吞运输的一般要求。与这些结果一致，我们发现标记的CDC-42/Cdc 42在C. elegans和哺乳动物细胞，表明在运输的调节直接功能。
In a genome-wide RNA-mediated interference screen for genes required in membrane traffic-including endocytic uptake, recycling from endosomes to the plasma membrane, and secretion-we identified 168 candidate endocytosis regulators and 100 candidate secretion regulators. Many of these candidates are highly conserved among metazoans but have not been previously implicated in these processes. Among the positives from the screen, we identified PAR-3, PAR-6, PKC-3 and CDC-42, proteins that are well known for their importance in the generation of embryonic and epithelial-cell polarity. Further analysis showed that endocytic transport in Caenorhabditis elegans coelomocytes and human HeLa cells was also compromised after perturbation of CDC-42/Cdc42 or PAR-6/Par6 function, indicating a general requirement for these proteins in regulating endocytic traffic. Consistent with these results, we found that tagged CDC-42/Cdc42 is enriched on recycling endosomes in C. elegans and mammalian cells, suggesting a direct function in the regulation of transport.