Glucose is a preferred metabolite in most mammalian cells, and proper regulation of uptake is critical for organism homeostasis. The glucose transporter 1 (GLUT1) is responsible for glucose uptake in a wide variety of cells and appears to be regulated in a tissue specific manner. Therefore, a better understanding of GLUT1 regulation within its various cellular environments is essential for developing therapeutic strategies to treat disorders associated with glucose homeostasis. Previous findings suggest that plasma membrane subdomains called lipid rafts may play a role in regulation of GLUT1 uptake activity. While studying this phenomenon in L929 mouse fibroblast cells, we observed that GLUT1 associates with a low density lipid microdomain distinct from traditionally-defined lipid rafts. These structures are not altered by cholesterol removal with methyl-β-cyclodextrin and lack resistance to cold Triton X-100 extraction. Our data indicate that the GLUT1-containing membrane microdomains in L929 cells, as well as GLUT1's basal activity, are instead sphingolipid-dependent, being sensitive to both myriocin and sphingomyelinase treatment. These microdomains appear to be organized primarily by their lipid composition, as disruption of the actin cytoskeleton or microtubules does not alter the association of GLUT1 with them. Furthermore, the association of GLUT1 with these microdomains appears not to require palmitoylation or glycosylation, as pharmacologic inhibition of these processes had no impact on GLUT1 density in membrane fractions. Importantly, we find no evidence that GLUT1 is actively translocated into or out of low density membrane fractions in response to acute activation in L929 cell.

中文翻译：

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GLUT1与L929小鼠成纤维细胞中鞘脂组织的，胆固醇独立的域相关。

葡萄糖是大多数哺乳动物细胞中的首选代谢产物，而摄取的适当调节对于机体动态平衡至关重要。葡萄糖转运蛋白1（GLUT1）负责各种细胞中的葡萄糖摄取，并且似乎以组织特异性的方式受到调节。因此，更好地了解其各种细胞环境中的GLUT1调节对于开发治疗与葡萄糖稳态相关的疾病的治疗策略至关重要。先前的发现表明，称为脂筏的质膜亚域可能在调节GLUT1摄取活性中发挥作用。在研究L929小鼠成纤维细胞中的这种现象时，我们观察到GLUT1与不同于传统定义的脂质筏的低密度脂质微结构域相关。这些结构不会被甲基-β-环糊精去除胆固醇而改变，并且对冷Triton X-100提取物没有抵抗力。我们的数据表明，L929细胞中含有GLUT1的膜微区以及GLUT1的基础活性是鞘脂依赖性的，对myriocin和鞘磷脂酶均敏感。这些微区似乎主要由其脂质组成来组织，因为肌动蛋白细胞骨架或微管的破坏不会改变GLUT1与它们的结合。此外，GLUT1与这些微域的关联似乎不需要棕榈酰化或糖基化，因为这些过程的药理学抑制作用对膜部分中的GLUT1密度没有影响。重要的，