Golgin-160 is required for the Golgi membrane sorting of the insulin-responsive glucose transporter GLUT4 in adipocytes.
Golgin-160 is required for the Golgi membrane sorting of the insulin-responsive glucose transporter GLUT4 in adipocytes.
复制标题
脂肪细胞中胰岛素响应性葡萄糖转运蛋白 GLUT4 的高尔基膜分选需要 Golgin-160。
DOI：
10.1091/mbc.e06-05-0386
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发表时间：
2006
影响因子：
3.3
通讯作者：
Pessin,JeffreyE
中科院分区：
文献类型：
--
作者：
Williams,Dumaine;Hicks,StuartW;Machamer,CarolynE;Pessin,JeffreyE
外周高尔基体蛋白 golgin-160 在 3T3L1 脂肪生成过程中被诱导，主要定位于高尔基体池，与反高尔基体网络 (TGN) 不同，其总体分布与 p115 相似。小干扰RNA（siRNA）介导的golgin-160蛋白减少导致质膜上胰岛素反应性氨基肽酶（IRAP）和胰岛素调节葡萄糖转运蛋白（GLUT4）的积累增加，同时基础状态下葡萄糖摄取增加。 GLUT4 的重新分布通过表达 siRNA 抗性 golgin-160 cDNA 来挽救。质膜 GLUT4 的基础状态积累是由于胞吐速率增加而发生的，而对胞吞速率没有任何显着影响。在没有golgin-160的情况下，GLUT4向质膜的运输与TGN/高尔基体分选无关，因为它不再受到显性干扰高尔基体定位的、含有γ-耳的ARF结合蛋白突变体的表达的抑制，并且与凝集素麦芽凝集素的结合减少。此外，氨基末端头结构域（氨基酸1-393）的表达对GLUT4或IRAP的分布或胰岛素调节的运输没有显着影响。相反，羧基α螺旋区（393-1498）的表达抑制胰岛素刺激的GLUT4和IRAP易位，但对组成型膜运输蛋白、转铁蛋白受体或水泡性口炎病毒G蛋白的分选没有影响。总之，这些数据表明，golgin-160 在引导胰岛素调节的运输蛋白流向脂肪细胞中的胰岛素反应区室方面发挥着重要作用。
The peripheral Golgi protein golgin-160 is induced during 3T3L1 adipogenesis and is primarily localized to the Golgi cisternae distinct from thetrans-Golgi network (TGN) in a general distribution similar to p115. Small interfering RNA (siRNA)-mediated reduction in golgin-160 protein resulted in an increase accumulation of the insulin-responsive amino peptidase (IRAP) and the insulin-regulated glucose transporter (GLUT4) at the plasma membrane concomitant with enhanced glucose uptake in the basal state. The redistribution of GLUT4 was rescued by expression of a siRNA-resistant golgin-160 cDNA. The basal state accumulation of plasma membrane GLUT4 occurred due to an increased rate of exocytosis without any significant effect on the rate of endocytosis. This GLUT4 trafficking to the plasma membrane in the absence of golgin-160 was independent of TGN/Golgi sorting, because it was no longer inhibited by the expression of a dominant-interfering Golgi-localized, γ-ear–containing ARF-binding protein mutant and displayed reduced binding to the lectin wheat germ agglutinin. Moreover, expression of the amino terminal head domain (amino acids 1–393) had no significant effect on the distribution or insulin-regulated trafficking of GLUT4 or IRAP. In contrast, expression of carboxyl α helical region (393–1498) inhibited insulin-stimulated GLUT4 and IRAP translocation, but it had no effect on the sorting of constitutive membrane trafficking proteins, the transferrin receptor, or vesicular stomatitis virus G protein. Together, these data demonstrate that golgin-160 plays an important role in directing insulin-regulated trafficking proteins toward the insulin-responsive compartment in adipocytes.