Caenorhabditis elegans num-1 negatively regulates endocytic recycling
Caenorhabditis elegans num-1 negatively regulates endocytic recycling
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DOI：
10.1534/genetics.108.087247
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发表时间：
2008-05-01
期刊：
影响因子：
3.3
通讯作者：
Tuck, Simon
中科院分区：
文献类型：
--
作者：
Nilsson, Lars;Conradt, Barbara;Tuck, Simon
通过内吞作用进入细胞的大部分物质通过内吞再循环途径迅速返回质膜。尽管回收对于细胞膜受体和脂质的正确定位至关重要，但调节回收的分子机制仅被部分了解。在这里，我们发现在线虫 Numb 同源物 NUM-1A 会抑制秀丽隐杆线虫的内吞再循环。 NUM-1A::GFP 融合蛋白定位于许多极化上皮细胞的基底外侧表面，包括皮下组织和肠道。我们发现，增加的 NUM-1A 水平会导致这些细胞的形态缺陷，类似于 rme-1 功能丧失突变引起的缺陷，rme-1 是秀丽隐杆线虫和人类中循环的正调节因子。我们描述了缺乏 num-1A 活性的蠕虫的分离，并表明，与 NUM-1A 负调节肠道循环的模型一致，num-1A 功能的丧失绕过了 RME-1 的要求。 rab-10 的遗传上位性分析表明，num-1A 功能的丧失不会影响内吞作用对物质的摄取，而是抑制 rab-10 下游的基底侧循环，这是回收途径早期所需的。
Much of the material taken into cells by endocytosis is rapidly returned to the plasma membrane by the endocytic recycling pathway. Although recycling is vital for the correct localization of cell membrane receptors and lipids, the molecular mechanisms that regulate recycling are only partially understood. Here we show that in Caenorhabditis elegans endocytic recycling is inhibited by NUM-1A, the nematode Numb homolog. NUM-1A::GFP fusion protein is localized to the baso-lateral Surfaces of many polarized epithelial cells, including the hypodermis and the intestine. We show that increased NUM-1A levels cause morphological defects in these cells similar to those caused by loss-of-function mutations in rme-1, a positive regulator of recycling in both C. elegans and mannuals. We describe the isolation of worms lacking num-1A activity and show that, consistent with a model in which NUM-1A negatively regulates recycling in the intestine, loss of num-1A function bypasses the requirement for RME-1. Genetic epistasis analysis with rab-10, which is required at an early part of the recycling pathway, suggests that loss of num-1A function does not affect the uptake of material by endocytosis but rather inhibits baso-lateral recycling downstream of rab-10.