Hnasko Robert, Lisanti Michael P
Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, The Bronx, NY 10461, USA.
Mol Interv. 2003 Dec;3(8):445-64. doi: 10.1124/mi.3.8.445.
Caveolae, plasma membrane invaginations that serve as membrane organizing centers, are found in most cell types, but are enriched in adipocytes, endothelial cells, and myocytes. Three members of the caveolin family (Cav-1, -2, and -3) are essential for the formation of caveolae. Specialized motifs in the caveolin proteins function to recruit lipids and proteins to caveolae for participation in intracellular trafficking of cellular components and operation in signal transduction. Mutations in the gene encoding CAV-1 are associated with the development and progression of breast cancers, whereas mutations in the CAV-3 gene result in Rippling Muscle Disease and a form of Limb-Girdle Muscular Dystrophy. The generation of caveolin-null mice has confirmed the essential role of these proteins in caveolae biogenesis and in the pathophysiology of diverse tissues. Caveolin-null mice provide new animal models for studying the pathogenesis of a number of human diseases, including cancer, diabetes, atherosclerosis, restrictive lung disease and pulmonary fibrosis, cardiomyopathy, muscular dystrophy, and bladder dysfunction.
小窝是作为膜组织中心的质膜内陷结构，存在于大多数细胞类型中，但在脂肪细胞、内皮细胞和心肌细胞中更为丰富。小窝蛋白家族的三个成员（Cav-1、-2和-3）对小窝的形成至关重要。小窝蛋白中的特殊基序可将脂质和蛋白质招募到小窝中，参与细胞成分的细胞内运输以及信号转导过程。编码CAV-1的基因突变与乳腺癌的发生和发展有关，而CAV-3基因突变则导致波纹肌病和一种肢带型肌营养不良症。小窝蛋白缺失小鼠的产生证实了这些蛋白质在小窝生物发生以及多种组织的病理生理学中的重要作用。小窝蛋白缺失小鼠为研究包括癌症、糖尿病、动脉粥样硬化、限制性肺病和肺纤维化、心肌病、肌营养不良症以及膀胱功能障碍在内的多种人类疾病的发病机制提供了新的动物模型。
