Identification of an N-acetylglucosamine transporter that mediates hyphal induction in Candida albicans
Identification of an N-acetylglucosamine transporter that mediates hyphal induction in Candida albicans
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DOI：
10.1091/mbc.e06-10-0931
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发表时间：
2007-03-01
影响因子：
3.3
通讯作者：
Konopka, James B.
中科院分区：
文献类型：
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作者：
Alvarez, Francisco J.;Konopka, James B.
糖N-乙酰氨基葡萄糖(GlcNAc)在从细菌到人类的多种生物的营养感知和细胞调节中发挥着重要作用。在真菌病原菌白色念珠菌中，GlcNAc诱导了从萌发到菌丝生长的形态转变。对GlcNAc诱导的芽和菌丝质膜蛋白进行蛋白质组学比较，发现一种新的菌丝蛋白(Ngt1)，与主要的转运蛋白促进超家族相似。经GlcNAc诱导后，在质膜上检测到Ngt1-GFP融合，但没有检测到其他相关糖的融合。巨噬细胞吞噬也能诱导NGT1-GFP，提示GlcNAc反应在信号进入吞噬溶酶体中起作用。NGT1是有效摄取GlcNAc和在低浓度GlcNAc下诱导菌丝生长所必需的。高浓度的GlcNAc可以绕过NGT1诱导菌丝的需要，这表明细胞内GlcNAc水平的升高可以诱导菌丝的形成。NGT1在酿酒酵母中的表达促进了对GlcNAc的摄取，表明NGT1直接作为GlcNAc转运体发挥作用。Ngt1介导的转运是特异的，因为其他糖不能竞争GlcNAc的摄取。因此，Ngt1代表了第一个被发现的真核细胞GlcNAc转运蛋白。从酵母到哺乳动物等多种真核生物基因组序列中NGT1同源物的存在表明，它们也可能在GlcNAc调控的细胞过程中发挥作用，包括那些导致癌症和糖尿病等重要疾病的过程。
The sugar N-acetylglucosamine (GlcNAc) plays an important role in nutrient sensing and cellular regulation in a wide range of organisms from bacteria to humans. In the fungal pathogen Candida albicans, GlcNAc induces a morphological transition from budding to hyphal growth. Proteomic comparison of plasma membrane proteins from buds and from hyphae induced by GlcNAc identified a novel hyphal protein (Ngt1) with similarity to the major facilitator superfamily of transporters. An Ngt1-GFP fusion was detected in the plasma membrane after induction with GlcNAc, but not other related sugars. Ngt1-GFP was also induced by macrophage phagocytosis, suggesting a role for the GlcNAc response in signaling entry into phagolysosomes. NGT1 is needed for efficient GlcNAc uptake and for the ability to induce hyphae at low GlcNAc concentrations. High concentrations of GlcNAc could bypass the need for NGT1 to induce hyphae, indicating that elevated intracellular levels of GlcNAc induce hyphal formation. Expression of NGT1 in Saccharomyces cerevisiae promoted GlcNAc uptake, indicating that Ngt1 acts directly as a GlcNAc transporter. Transport mediated by Ngt1 was specific, as other sugars could not compete for the uptake of GlcNAc. Thus, Ngt1 represents the first eukaryotic GlcNAc transporter to be discovered. The presence of NGT1 homologues in the genome sequences of a wide range of eukaryotes from yeast to mammals suggests that they may also function in the cellular processes regulated by GlcNAc, including those that underlie important diseases such as cancer and diabetes.