Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae
Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae
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DOI：
10.1128/mcb.22.7.2329-2344.2002
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发表时间：
2002-04-01
影响因子：
5.3
通讯作者：
Lisanti, MP
中科院分区：
文献类型：
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作者：
Razani, B;Wang, XB;Lisanti, MP
小窝蛋白-2是小窝蛋白基因家族中的一员，功能未知。尽管小窝蛋白-2在许多细胞类型(尤其是脂肪细胞和内皮细胞)中与小窝蛋白-1共表达和异位寡聚，但小窝蛋白-2传统上被认为是被广泛研究的小窝蛋白-1不可或缺的结构伙伴。现在，我们通过在小鼠中以小窝蛋白-2基因(Cav-2)为靶点，直接阐述小窝蛋白-2的功能意义。在缺少小凹蛋白-2蛋白表达的情况下，小窝仍然形成，小窝-1保持其在质膜小窝中的定位，尽管在某些组织中小窝-1部分失稳并显示出适度的蛋白质水平降低。尽管有完整的肺泡膜系统，但Cav-2缺失的肺实质表现为高细胞，肺泡间隔增厚，内皮细胞数量增加。由于这些病理变化，这些Cav-2基因缺失的小鼠明显缺乏运动耐受性。有趣的是，这些Cav-2缺失的表型与我们和其他人最近报道的Cav-1缺失小鼠的表型相同。由于在Cav-1基因缺失的小鼠中，小窝蛋白-2的表达也严重减少，我们得出结论，小窝蛋白-2缺乏是这种肺部疾病的明显罪魁祸首。我们对小凹蛋白-1缺陷小鼠中观察到的几种不同表型(即异常的血管反应和脂类平衡改变)的分析表明，Cav-2缺失的小鼠没有表现出任何其他表型，这表明小窝蛋白-2在肺功能中具有选择性作用。综上所述，我们的数据首次显示了小窝蛋白-2在哺乳动物生理学中独立于小窝蛋白-1的特定作用。
Caveolin-2 is a member of the caveolin gene family with no known function. Although caveolin-2 is coexpressed and heterooligomerizes with caveolin-1 in many cell types (most notably adipocytes and endothelial cells), caveolin-2 has traditionally been considered the dispensable structural partner of the widely studied caveolin-1. We now directly address the functional significance of caveolin-2 by genetically targeting the caveolin-2 locus (Cav-2) in mice. In the absence of caveolin-2 protein expression, caveolae still form and caveolin-1 maintains its localization in plasma membrane caveolae, although in certain tissues caveolin-1 is partially destabilized and shows modestly diminished protein levels. Despite an intact caveolar membrane system, the Cav-2-null lung parenchyma shows hypercellularity, with thickened alveolar septa and an increase in the number of endothelial cells. As a result of these pathological changes, these Cav-2-null mice are markedly exercise intolerant. Interestingly, these Cav-2-null phenotypes are identical to the ones we and others have recently reported for Cav-1-null mice. As caveolin-2 expression is also severely reduced in Cav-1-null mice, we conclude that caveolin-2 deficiency is the clear culprit in this lung disorder. Our analysis of several different phenotypes observed in caveolin-1-deficient mice (i.e., abnormal vascular responses and altered lipid homeostasis) reveals that Cav-2-null mice do not show any of these other phenotypes, indicating a selective role for caveolin-2 in lung function. Taken together, our data show for the first time a specific role for caveolin-2 in mammalian physiology independent of caveolin-1.