Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice
Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice
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DOI：
10.1126/science.1062688
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发表时间：
2001-09-28
期刊：
影响因子：
56.9
通讯作者：
Kurzchalia, TV
中科院分区：
文献类型：
--
作者：
Drab, M;Verkade, P;Kurzchalia, TV
小泡是一种质膜内陷，可能在许多细胞过程中发挥重要作用，包括运输、信号传导和肿瘤抑制。通过靶向破坏小窝蛋白-1（小窝的主要蛋白质成分），我们产生了缺乏小窝的小鼠。这种细胞器的缺失会损害心血管系统中的一氧化氮和钙信号，导致内皮依赖性松弛、收缩性和肌原性张力维持的异常。此外，基因敲除动物的肺显示内皮细胞增殖和纤维化失控导致肺泡间隔增厚，导致caveolin-1破坏小鼠严重的身体限制。因此，小泡蛋白-1和小泡在组织细胞中的多种信号通路中起着重要作用。
Caveolae are plasma membrane invaginations that may play an important role in numerous cellular processes including transport, signaling, and tumor suppression. By targeted disruption of caveolin-1, the main protein component of caveolae, we generated mice that lacked caveolae. The absence of this organelle impaired nitric oxide and calcium signaling in the cardiovascular system, causing aberrations in endothelium-dependent relaxation, contractility, and maintenance of myogenic tone. In addition, the lungs of knockout animals displayed thickening of alveolar septa caused by uncontrolled endothelial cell proliferation and fibrosis, resulting in severe physical limitations in caveolin-1-disrupted mice. Thus, caveolin-1 and caveolae play a fundamental role in organizing multiple signaling pathways in the cell.