Similar [DE]XXXL[LI] Motifs Differentially Target GLUT8 and GLUT12 in Chinese Hamster Ovary Cells
Similar [DE]XXXL[LI] Motifs Differentially Target GLUT8 and GLUT12 in Chinese Hamster Ovary Cells
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DOI：
10.1111/j.1600-0854.2008.00866.x
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发表时间：
2009-03-01
期刊：
影响因子：
4.5
通讯作者：
Moley, Kelle H.
中科院分区：
文献类型：
--
作者：
Flessner, Lauren B.;Moley, Kelle H.
葡萄糖跨细胞膜的转运是由促进性葡萄糖转运体(GLUT)介导的。最近发现的III型GLUT12主要在胰岛素敏感的组织中表达，如心脏、脂肪和骨骼肌。我们检测了GLUT12在中国仓鼠卵巢和稳定表达小鼠GLUT12的人胚胎肾293细胞中的亚细胞定位。我们先前已经证明，另一个III类GLUT8包含一个[DE]XXXL[Li]基序，该基序将其导向晚期内体/溶酶体间隔。尽管GLUT12的氨基末端也有这个高度保守的基序，但它并不与GLUT8共定位。相反，GLUT12存在于高尔基体网络和质膜(PM)。此外，GLUT8和GLUT12在贩运方面与PM有很大不同虽然GLUT8在细胞表面的表达后被内化，但GLUT12在很大程度上仍然与PM有关为了进一步探索转运机制，我们创建了突变结构来探索GLUT12的S NH2末端二亮氨酸基序在调节其细胞内分选中的潜在作用。我们发现[DE]XXXL[Li]基序中的GPN和LL残基都影响GLUT12的细胞表面表达，并得出结论，GLUT12的细胞内分选机制与GLUT8的分选机制不同。
The transport of glucose across cell membranes is mediated by facilitative glucose transporters (GLUTs). The recently identified class III GLUT12 is predominantly expressed in insulin-sensitive tissues such as heart, fat and skeletal muscle. We examined the subcellular localization of GLUT12 in Chinese hamster ovary and human embryonic kidney 293 cells stably expressing murine GLUT12. We have previously shown that another class III GLUT8 contains a [DE]XXXL[LI] motif that directs it to late endosomal/lysosomal compartments. Despite also having this highly conserved motif in its amino terminus, GLUT12 does not colocalize with GLUT8. Rather, GLUT12 resides in the Golgi network and at the plasma membrane (PM). Furthermore, GLUT8 and GLUT12 exhibit dramatic differences in trafficking from the PM. Whereas GLUT8 is internalized following its expression at the cell surface, GLUT12 remains largely associated with the PM. To further explore the trafficking mechanisms, we created mutant constructs to explore the potential role of GLUT12's NH2-terminal dileucine motif in regulating its intracellular sorting. We show that both the GPN and the LL residues within the [DE]XXXL[LI] motif influence the cell surface expression of GLUT12 and conclude that the mechanisms governing the intracellular sorting of GLUT12 are distinct from those regulating the sorting of GLUT8.