Induction of caveolin during adipogenesis and association of GLUT4 with caveolin-rich vesicles.
Induction of caveolin during adipogenesis and association of GLUT4 with caveolin-rich vesicles.
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DOI：
10.1083/jcb.127.5.1233
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发表时间：
1994-12
影响因子：
7.8
通讯作者：
Lodish, H F
中科院分区：
文献类型：
--
作者：
Scherer, P E;Lisanti, M P;Baldini, G;Sargiacomo, M;Mastick, C C;Lodish, H F
小窝，也被称为质膜小泡，是一种小的、烧瓶状的、非笼罩在质膜上的内陷。小窝是构成小窝条纹外套的细丝的主要成分。使用小窝蛋白作为细胞器的标记蛋白，我们发现脂肪组织是迄今为止已发现的最丰富的小窝来源。在3T3-L1成纤维细胞向脂肪细胞分化的过程中，小窝蛋白的mRNA和蛋白被强烈地诱导；在脂肪形成过程中，富含小窝蛋白的膜域的蛋白质组成的复杂性也急剧增加。大约10%-15%的胰岛素反应葡萄糖转运体GLUT4存在于这种富含小窝蛋白的组分中，免疫分离的含有GLUT4的小泡也含有小窝蛋白。然而，在未受刺激的脂肪细胞中，大多数小窝蛋白与质膜分离，而大多数GLUT4与低密度微体有关。在3T3-L1脂肪细胞中加入胰岛素后，与富含小窝蛋白的膜结构域相关的GLUT4的数量显著增加，与质膜相关的小窝蛋白的数量增加，与低密度微粒体相关的小窝蛋白的数量减少。当胰岛素刺激3T3-L1脂肪细胞时，小窝蛋白不会发生磷酸化改变。然而，在胰岛素治疗后，它与一种32kD的磷酸化蛋白有关。因此，小窝可能在GLUT4进入或离开质膜的囊泡运输中发挥重要作用。3T3-L1脂肪细胞提供了一个诱人的系统来研究小凹在几个细胞运输和信号事件中的功能。
Caveolae, also termed plasmalemmal vesicles, are small, flask-shaped, non-clathrin-coated invaginations of the plasma membrane. Caveolin is a principal component of the filaments that make up the striated coat of caveolae. Using caveolin as a marker protein for the organelle, we found that adipose tissue is the single most abundant source of caveolae identified thus far. Caveolin mRNA and protein are strongly induced during differentiation of 3T3-L1 fibroblasts to adipocytes; during adipogenesis there is also a dramatic increase in the complexity of the protein composition of caveolin-rich membrane domains. About 10- 15% of the insulin-responsive glucose transporter GLUT4 is found in this caveolin-rich fraction, and immuno-isolated vesicles containing GLUT4 also contain caveolin. However, in non-stimulated adipocytes the majority of caveolin fractionates with the plasma membrane, while most GLUT4 associates with low-density microsomes. Upon addition of insulin to 3T3-L1 adipocytes, there is a significant increase in the amount of GLUT4 associated with caveolin-rich membrane domains, an increase in the amount of caveolin associated with the plasma membrane, and a decrease in the amount of caveolin associated with low-density microsomes. Caveolin does not undergo a change in phosphorylation upon stimulation of 3T3-L1 adipocytes with insulin. However, after treatment with insulin it is associated with a 32-kD phosphorylated protein. Caveolae thus may play an important role in the vesicular transport of GLUT4 to or from the plasma membrane. 3T3-L1 adipocytes offer an attractive system to study the function of caveolae in several cellular trafficking and signaling events.