The GLUT (SLC2) family of membrane-associated transporters are described as glucose transporters. However, this family is divided into three classes and, though the regulated transporter activity of class I proteins is becoming better understood, class III protein functions continue to be obscure. We have cataloged the relative expression and splicing of SLC2 mRNA isomers in tumors and normal tissues, with a focus on breast tumors and cell lines. mRNA for the class III protein GLUT8 is the predominant SLC2 species expressed alongside GLUT1 in many tissues, but GLUT8 mRNA exists mostly as an untranslated splice form in tumors. We confirm that GLUT8 is not presented at the cell surface and does not transport glucose directly. However, we reveal a lysosome-dependent reaction that cleaves the GLUT8 protein and releases the carboxy-terminal peptide to a separate vesicle population. Given the localization of GLUT8 at a major metabolic hub (the late endosomal/lysosomal interface) and its regulated cleavage reaction, we evaluated TXNIP-mediated hexosamine homeostasis and speculate that GLUT8 may function as a sensory component of this reaction.

中文翻译：

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GLUT8的可变剪接和切割

膜相关转运蛋白的GLUT（SLC2）家族被称为葡萄糖转运蛋白。但是，该家族分为三类，尽管人们对I类蛋白的调节转运蛋白活性有了更好的了解，但III类蛋白的功能仍然不清楚。我们已经对SLC2 mRNA异构体在肿瘤和正常组织中的相对表达和剪接进行了分类，重点研究了乳腺肿瘤和细胞系。III类蛋白GLUT8的mRNA是主要的SLC2GLUT1在许多组织中与其他物种一起表达，但GLUT8 mRNA在肿瘤中主要以未翻译的剪接形式存在。我们确认GLUT8没有出现在细胞表面，也没有直接转运葡萄糖。但是，我们揭示了裂解GLUT8蛋白并释放羧基末端肽到单独的囊泡群体的溶酶体依赖性反应。鉴于GLUT8定位在主要的代谢枢纽（晚期的内体/溶酶体界面）及其调控的裂解反应，我们评估了TXNIP介导的己糖稳态，并推测GLUT8可能是该反应的感觉成分。