Cell-type and tissue-specific expression of caveolin-2 - Caveolins 1 and 2 co-localize and form a stable hetero-oligomeric complex in vivo
Cell-type and tissue-specific expression of caveolin-2 - Caveolins 1 and 2 co-localize and form a stable hetero-oligomeric complex in vivo
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DOI：
10.1074/jbc.272.46.29337
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发表时间：
1997-11-14
影响因子：
4.8
通讯作者：
Lisanti, MP
中科院分区：
文献类型：
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作者：
Scherer, PE;Lewis, RY;Lisanti, MP
细胞膜小窝是细胞膜上的一个微区，参与细胞信号转导分子的组织和区室化。小窝蛋白（Caveolin）是一种分子量为21-24-kDa的膜蛋白，是细胞膜小窝的主要结构成分。最近，我们和其他实验室鉴定了一个小窝蛋白相关蛋白家族;小窝蛋白又被重新命名为小窝蛋白-1。在这里，我们研究了小窝蛋白-2的细胞类型和组织特异性表达。为此，我们制备了一种新的单特异性单克隆抗体探针，它只识别小窝蛋白-2，而不识别小窝蛋白-1和-3，对细胞和组织类型的调查表明，小窝蛋白-2在内皮细胞、平滑肌细胞、骨骼肌成肌细胞（L 6、BC 3 H1、C2 C12）、成纤维细胞和分化为脂肪细胞的3 T3-L1细胞中表达最丰富。这种小窝蛋白-2蛋白表达的模式最接近于小窝蛋白-1的细胞分布。与这些观察结果一致，用针对小窝蛋白-1或小窝蛋白-2的单特异性抗体进行的免疫共沉淀实验直接显示这些分子形成稳定的异源寡聚复合物，采用共聚焦激光扫描荧光显微镜的双标记研究进一步揭示了这种复合物在体内的相关性。我们的研究结果表明，小窝蛋白1和2是严格的共同定位在质膜和其他内部细胞膜，超微结构，这种模式的小窝蛋白-2的定位对应于小窝膜，如通过免疫电子显微镜所看到的，尽管这种严格的共同定位，似乎小窝蛋白-2表达的调节独立于小窝蛋白-1或小窝蛋白-1的表达而发生。尽管caveolin-1表达在NIH 3 T3细胞的致癌转化中下调，但caveolin-2蛋白水平保持不变。此外，caveolin-2蛋白水平在C2 C12细胞从成肌细胞分化为肌管的过程中保持不变，这些结果表明，窖蛋白1、2和3的表达水平可以响应于多种不同的细胞信号而独立地上调或下调。
Caveolae are microdomains of the plasma membrane that have been implicated in organizing and compartmentalizing signal transducing molecules, Caveolin, a 21-24-kDa integral membrane protein, is a principal structural component of caveolae membrane in vivo. Recently, we and other laboratories have identified a family of caveolin-related proteins; caveolin has been retermed caveolin-1.Here, we examine the cell type and tissue-specific expression of caveolin-2, For this purpose, we generated a novel mono-specific monoclonal antibody probe that recognizes only caveolin-2, but not caveolins-1 and -3, A survey of cell and tissue types demonstrates that the caveolin-2 protein is most abundantly expressed in endothelial cells, smooth muscle cells, skeletal myoblasts (L6, BC3H1, C2C12), fibroblasts, and 3T3-L1 cells differentiated to adipocytes. This pattern of caveolin-2 protein expression most closely resembles the cellular distribution of caveolin-1, In line with these observations, co-immunoprecipitation experiments with mono-specific antibodies directed against either caveolin-1 or caveolin-2 directly show that these molecules form a stable hetero-oligomeric complex, The in vivo relevance of this complex was further revealed by dual-labeling studies employing confocal laser scanning fluorescence microscopy. Our results indicate that caveolins 1 and 2 are strictly co localized within the plasma membrane and other internal cellular membranes, Ultrastructurally, this pattern of caveolin-2 localization corresponds to caveolae membranes as seen by immunoelectron microscopy, Despite this strict co-localization, it appears that regulation of caveolin-2 expression occurs independently of the expression of either caveolin-1 or caveolin-3 as observed using two different model cell systems, Although caveolin-1 expression is down-regulated in response to oncogenic transformation of NIH 3T3 cells, caveolin-2 protein levels remain unchanged, Also, caveolin-2 protein levels remain unchanged during the differentiation of C2C12 cells from myoblasts to myotubes, while caveolin-3 levels are dramatically induced by this process, These results suggest that expression levels of caveolins 1, 2, and 3 can be independently up-regulated or down-regulated in response to a variety of distinct cellular cues.