Deletion of cavin genes reveals tissue-specific mechanisms for morphogenesis of endothelial caveolae.

Deletion of cavin genes reveals tissue-specific mechanisms for morphogenesis of endothelial caveolae.
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DOI:
10.1038/ncomms2808
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发表时间:
2013
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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小窝在内皮细胞中非常丰富,被认为在内皮细胞生物学中具有重要作用。cavin蛋白是小窝的关键成分,在不同组织中表达量不同。在这里,我们使用基因敲除小鼠,以确定洞穴蛋白2和3在体内小窝形态发生的作用。cavin 2的缺失导致肺和脂肪组织中内皮小窝的缺失,但对心脏和其他组织中内皮小窝的丰度没有影响。cavin 2基因敲除小鼠内皮细胞形态学的变化与小窝丰度的变化相关。在检查的组织中形成小窝不需要Cavin 3。Cavin 2决定了cavin复合体的大小,并起到塑造小窝的作用。然而,Cavin 1对于小窝蛋白1的正常寡聚化是必需的。我们的数据显示,内皮细胞小窝是异质性的,并确定cavin 2作为这种异质性的决定因素。 Cavin蛋白是哺乳动物细胞膜小窝的关键组成部分,由四个基因以组织特异性方式表达。Gram汉森等人证明,不同组织内皮细胞中的小窝是显著异质的,并揭示了cavin 2在决定cavin复合物表观大小中的作用。
Caveolae are abundant in endothelial cells and are thought to have important roles in endothelial cell biology. The cavin proteins are key components of caveolae, and are expressed at varied amounts in different tissues. Here we use knockout mice to determine the roles of cavins 2 and 3 in caveolar morphogenesis in vivo. Deletion of cavin 2 causes loss of endothelial caveolae in lung and adipose tissue, but has no effect on the abundance of endothelial caveolae in heart and other tissues. Changes in the morphology of endothelium in cavin 2 null mice correlate with changes in caveolar abundance. Cavin 3 is not required for making caveolae in the tissues examined. Cavin 2 determines the size of cavin complexes, and acts to shape caveolae. Cavin 1, however, is essential for normal oligomerization of caveolin 1. Our data reveal that endothelial caveolae are heterogeneous, and identify cavin 2 as a determinant of this heterogeneity. Cavin proteins are key components of mammalian caveolae and are expressed from four genes in a tissue-specific manner. Gram Hansen et al. demonstrate that caveolae in the endothelia of different tissues are remarkably heterogeneous, and reveal a role for cavin 2 in determining the apparent size of cavin complexes.
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