The formation of an insulin-responsive vesicular cargo compartment is an early event in 3T3-L1 adipocyte differentiation

The formation of an insulin-responsive vesicular cargo compartment is an early event in 3T3-L1 adipocyte differentiation
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DOI:
10.1091/mbc.10.5.1581
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发表时间:
1999-05-01
影响因子:
3.3
通讯作者:
Pilch, PF
Pilch, PF
中科院分区:
生物学3区
文献类型:
--
作者:
El-Jack, AK;Kandror, KV;Pilch, PF

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分化的3 T3-L1细胞在从增殖的成纤维细胞向非增殖的脂肪细胞转化期间,胰岛素刺激的葡萄糖转运速率显著增加。在3 T3-L1细胞分化的第3天,基础葡萄糖转运和细胞表面转铁蛋白结合显著减少。这是伴随着形成一个独特的胰岛素反应囊泡池的细胞内葡萄糖转运蛋白1(GLUT 1)和转铁蛋白受体的蔗糖速度梯度评估。胰岛素应答性氨肽酶的细胞内分布在第3天首先容易检测到,此时其梯度分布和对胰岛素的应答与GLUT 1相同。随着分化时间的进一步延长,GLUT 4表达并靶向与其他三种蛋白质相同的胰岛素响应性囊泡。我们的数据是一致的概念,即一个独特的胰岛素敏感的囊泡货舱形成早期脂肪细胞分化,其形成之前GLUT 4的表达。该隔室的形成可能是由于组成型GLUT 1和转铁蛋白受体运输的分化依赖性抑制,使得内吞体后胰岛素应答囊泡群体大量增加或新形成。
Differentiating 3T3-L1 cells exhibit a dramatic increase in the rate of insulin-stimulated glucose transport during their conversion from proliferating fibroblasts to nonproliferating adipocytes. On day 3 of 3T3-L1 cell differentiation, basal glucose transport and cell surface transferrin binding are markedly diminished. This occurs concomitant with the formation of a distinct insulin-responsive vesicular pool of intracellular glucose transporter 1 (GLUT1) and transferrin receptors as assessed by sucrose velocity gradients. The intracellular distribution of the insulin-responsive aminopeptidase is first readily detectable on day 3, and its gradient profile and response to insulin at this time are identical to that of GLUT1. With further time of differentiation, GLUT4 is expressed and targeted to the same insulin-responsive vesicles as the other three proteins. Our data are consistent with the notion that a distinct insulin-sensitive vesicular cargo compartment forms early during fat call differentiation and its formation precedes GLUT4 expression. The development of this compartment may result from the differentiation-dependent inhibition of constitutive GLUT1 and transferrin receptor trafficking such that there is a large increase in, or the new formation of, a population of postendosomal, insulin-responsive vesicles.