FGT-1 is the major glucose transporter in C. elegans and is central to aging pathways.
FGT-1 is the major glucose transporter in C. elegans and is central to aging pathways.
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DOI：
10.1042/bj20131101
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发表时间：
2013-12-01
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影响因子：
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通讯作者：
Holman GD
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文献类型：
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作者：
Feng Y;Williams BG;Koumanov F;Wolstenholme AJ;Holman GD
秀丽隐杆线虫被广泛用作研究衰老、营养限制和通过胰岛素样肽和AGE-1 [衰老改变1; PI 3 K（磷酸肌醇3-激酶）的直向同源物]的β-2（异常dauer形成2）受体的信号传导之间关系的模型，但可能连接这些过程的葡萄糖转运蛋白的身份尚不清楚。我们意外地发现，在八个假定的GLUT（葡萄糖转运蛋白）样基因中，只有一个基因的两个剪接变体在卵母细胞表达系统中具有葡萄糖转运功能。我们将此基因命名为fgt-1（易化葡萄糖转运蛋白，同种型1）。我们发现，敲低fgt-1 RNA导致葡萄糖转运的损失和减少葡萄糖代谢的野生型蠕虫。C.因此，线虫在向C.优雅的。重要的是，敲低fgt-1导致的寿命延长与daf-2和age-1突变蠕虫中观察到的寿命延长相当，但不是累加的。本研究的结果与在C.并且该过程与DAF-2和AGE-1突变蠕虫中的长寿表型相关。我们认为fgt-1构成了营养限制和胰岛素样肽信号传导减少的寿命延长效应的共同轴。在C中，只有FGT 1A/B蛋白异构体作为葡萄糖转运蛋白起作用。优雅的。fgt-1 RNA的敲低导致葡萄糖转运的损失，降低葡萄糖代谢和延长寿命。因此，FGT-1葡萄糖转运蛋白在调节葡萄糖能量供应和寿命中起关键作用。
Caenorhabditis elegans is widely used as a model for investigation of the relationships between aging, nutrient restriction and signalling via the DAF-2 (abnormal dauer formation 2) receptor for insulin-like peptides and AGE-1 [ageing alteration 1; orthologue of PI3K (phosphoinositide 3-kinase)], but the identity of the glucose transporters that may link these processes is unknown. We unexpectedly find that of the eight putative GLUT (glucose transporter)-like genes only the two splice variants of one gene have a glucose transport function in an oocyte expression system. We have named this gene fgt-1 (facilitated glucose transporter, isoform 1). We show that knockdown of fgt-1 RNA leads to loss of glucose transport and reduced glucose metabolism in wild-type worms. The FGT-1 glucose transporters of C. elegans thus play a key role in glucose energy supply to C. elegans. Importantly, knockdown of fgt-1 leads to an extension of lifespan equivalent, but not additive, to that observed in daf-2 and age-1 mutant worms. The results of the present study are consistent with DAF-2 and AGE-1 signalling stimulating glucose transport in C. elegans and this process being associated with the longevity phenotype in daf-2 and age-1 mutant worms. We propose that fgt-1 constitutes a common axis for the lifespan extending effects of nutrient restriction and reduced insulin-like peptide signalling. Only the FGT1A/B protein isoforms function as glucose transporters in C. elegans. Knockdown of fgt-1 RNA leads to loss of glucose transport, reduced glucose metabolism and extended lifespan. FGT-1 glucose transporters therefore play a key role in regulated glucose energy supply and lifespan.