Lysosomal localization of GLUT8 in the testis--the EXXXLL motif of GLUT8 is sufficient for its intracellular sorting via AP1- and AP2-mediated interaction.
Lysosomal localization of GLUT8 in the testis--the EXXXLL motif of GLUT8 is sufficient for its intracellular sorting via AP1- and AP2-mediated interaction.
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DOI：
10.1111/j.1742-4658.2009.07089.x
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发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
Augustin R
中科院分区：
文献类型：
--
作者：
Diril MK;Schmidt S;Krauss M;Gawlik V;Joost HG;Schürmann A;Haucke V;Augustin R
III类糖转运促进剂GLUT8在异源表达系统中与溶酶体蛋白LAMP1共定位。GLUT8携带[D/E]XXXL[L/I]型二亮氨酸分选信号，该信号被认为通过与网格蛋白连接蛋白（AP）复合物的相互作用将蛋白质保留在内体/溶酶体腔室中。然而，关于内源性GLUT8的亚细胞定位及其与二亮氨酸基序相互作用的衔接蛋白的矛盾发现已经被描述。在这里，我们证明内源性GLUT8定位于精母细胞和精母细胞的内体/溶酶体晚期腔室，并且接头复合物AP1和AP2，而不是AP3或AP4，与其n端细胞内结构域（NICD）相互作用。此外，GLUT8 NICD与IL-2受体α链（IL-2受体α链）蛋白的无尾腔结构域融合，将该蛋白靶向到细胞膜内，表明其n端二亮氨酸信号足以用于内体/溶酶体靶向转运蛋白。GLUT8的定位和靶向与溶酶体蛋白的分选机制有着惊人的相似之处。因此，我们认为GLUT8在迄今尚未探索的底物跨细胞膜运输中的潜在作用。结构化数字摘要：MINT-7035377: GLUT8 （uniprotkb:Q9JIF3）通过下拉（MI:0096）与AP2 （uniprotkb:P62944）进行物理交互（MI:0915）与AP1 （uniprotkb:O43747）进行物理交互（MI:0915） MINT-7035273: GLUT8 （uniprotkb:Q9JIF3）通过下拉（MI:0096）与AP1 （uniprotkb:P22892）进行物理交互（MI:0915） MINT-7035235：GLUT8 （uniprotkb:Q9JIF3）与AP1 （uniprotkb:Q8R525）物理相互作用（MI:0915）通过下拉（MI:0096）与AP2 （uniprotkb:Q9JIF3）物理相互作用（MI:0915）通过下拉（MI:0096） MINT-7035789, MINT-7035807: lamp1 （uniprotkb:P11438）和GLUT8 （uniprotkb:Q9JIF3）共定位（MI:0403）通过荧光显微镜（MI:0416） MINT-7039929, MINT-7039945；lamp2（单蛋白：P17047）和GLUT8（单蛋白：Q9JIF3）通过荧光显微镜（MI:0416）共定位（MI:0403）
The class III sugar transport facilitator GLUT8 co-localizes with the lysosomal protein LAMP1 in heterologous expression systems. GLUT8 carries a [D/E]XXXL[L/I]-type dileucine sorting signal that has been postulated to retain the protein in an endosomal/lysosomal compartment via interactions with clathrin adaptor protein (AP) complexes. However, contradictory findings have been described regarding the subcellular localization of the endogenous GLUT8 and the adaptor proteins that interact with its dileucine motif. Here we demonstrate that endogenous GLUT8 is localized in a late endosomal/lysosomal compartment of spermatocytes and spermatids, and that the adaptor complexes AP1 and AP2, but not AP3 or AP4, interact with its N-terminal intracellular domain (NICD). In addition, fusion of the GLUT8 NICD to the tailless lumenal domain of the IL-2 receptor alpha chain (TAC) protein (interleukin-2 receptor α chain) targeted the protein to intracellular membranes, indicating that its N-terminal dileucine signal is sufficient for endosomal/lysosomal targeting of the transporter. The localization and targeting of GLUT8 show striking similarities to sorting mechanisms reported for lysosomal proteins. Therefore, we suggest a potential role for GLUT8 in the so far unexplored substrate transport across intracellular membranes. Structured digital abstract MINT-7035377: GLUT8 (uniprotkb:Q9JIF3) physically interacts (MI:0915) with AP2 (uniprotkb:P62944) by pull down (MI:0096) MINT-7035218: GLUT8 (uniprotkb:Q9JIF3) physically interacts (MI:0915) with AP1 (uniprotkb:O43747) by pull down (MI:0096) MINT-7035273: GLUT8 (uniprotkb:Q9JIF3) physically interacts (MI:0915) with AP1 (uniprotkb:P22892) by pull down (MI:0096) MINT-7035235: GLUT8 (uniprotkb:Q9JIF3) physically interacts (MI:0915) with AP1 (uniprotkb:Q8R525) by pull down (MI:0096) MINT-7035360: GLUT8 (uniprotkb:Q9JIF3) physically interacts (MI:0915) with AP2 (uniprotkb:Q9DBG3) by pull down (MI:0096) MINT-7035789, MINT-7035807: lamp1 (uniprotkb:P11438) and GLUT8 (uniprotkb:Q9JIF3) colocalize (MI:0403) by fluorescence microscopy (MI:0416) MINT-7039929, MINT-7039945: lamp2 (uniprotkb:P17047) and GLUT8 (uniprotkb:Q9JIF3) colocalize (MI:0403) by fluorescence microscopy (MI:0416)
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影响因子：
7.8
作者：
Janvier, Katy;Kato, Yukio;Boehm, Markus;Rose, Jeremy R;Martina, Jose A;Kim, Bong-Yoon;Venkatesan, Sundararajan;Bonifacino, Juan S
通讯作者：
Bonifacino, Juan S
影响因子：
5.3
作者：
Fehr, M;Takanaga, H;Frommer, WB
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Frommer, WB
影响因子：
4.5
作者：
Flessner, Lauren B.;Moley, Kelle H.
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影响因子：
2.2
作者：
Gomez, O.;Ballester, B.;Terrado, J.
通讯作者：
Terrado, J.
影响因子：
4.8
作者：
Ibberson, M;Uldry, M;Thorens, B
通讯作者：
Thorens, B