The WD40 and FYVE domain containing protein 2 defines a class of early endosomes necessary for endocytosis
The WD40 and FYVE domain containing protein 2 defines a class of early endosomes necessary for endocytosis
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DOI：
10.1073/pnas.0508832103
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发表时间：
2006-08-08
影响因子：
11.1
通讯作者：
Corvera, Silvia
中科院分区：
文献类型：
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作者：
Hayakawa, Akira;Leonard, Deborah;Corvera, Silvia
FYVE结构域对3-磷酸磷脂酰肌醇具有高特异性和亲和性。它存在于人类大约30种蛋白质中，其中一些涉及从早期核内体融合到通过tgf - β受体进行信号转导的功能。为了进一步了解该蛋白家族的生物学作用，我们转向秀丽隐杆线虫，该线虫仅含有12个基因，预测编码磷脂酰肌醇3-磷酸结合，含FYVE结构域的蛋白，所有这些蛋白在人类基因组中都有同源物。每一种蛋白质都是通过RNA干扰单独靶向的。其中一种蛋白WDFY2在沉默时对内吞作用产生强烈的抑制作用。WDFY2含有WD40基序和一个FYVE结构域，在物种间高度保守，定位于距离质膜100 nm内的一组小内体。这些内体参与转铁蛋白摄取，但缺乏经典的内体标记物Rab5和EEA1。哺乳动物细胞中siRNA对WDFY2的沉默会损害转铁蛋白的内吞作用。这些研究揭示了WDFY2在内吞作用中的重要、保守作用，以及与质膜密切相关的早期内体亚群的存在，它们可能构成内化货物内吞加工的第一阶段。
The FYVE domain binds with high specificity and avidity to phosphatidylinositol 3-phosphate. It is present in approximate to 30 proteins in humans, some of which have been implicated in functions ranging from early endosome fusion to signal transduction through the TGF-beta receptor. To develop a further understanding of the biological roles of this protein family, we turned to the nematode Caenorhabditis elegans, which contains only 12 genes predicted to encode for phosphatidylinositol 3-phosphate binding, FYVE domain-containing proteins, all of which have homologs in the human genome. Each of these proteins was targeted individually by RNA interference. One protein, WDFY2, produced a strong inhibition of endocytosis when silenced. WDFY2 contains WD40 motifs and a FYVE domain, is highly conserved between species, and localizes to a set of small endosomes that reside within 100 nm from the plasma membrane. These endosomes are involved in transferrin uptake but lack the classical endosomal markers Rab5 and EEA1. Silencing of WDFY2 by siRNA in mammalian cells impaired transferrin endocytosis. These studies reveal the important, conserved role of WDFY2 in endocytosis, and the existence of a subset of early endosomes, closely associated with the plasma membrane, that may constitute the first stage of endocytic processing of internalized cargo.