*Department of Medicine and Department of Anesthesiology, University of California at San Diego, School of Medicine, San Diego, California, USA; U.S. Veterans Administration, San Diego Healthcare System, San Diego, California, USA; and Maastricht University, Maastricht, The Netherlands.
*Department of Medicine and Department of Anesthesiology, University of California at San Diego, School of Medicine, San Diego, California, USA; U.S. Veterans Administration, San Diego Healthcare System, San Diego, California, USA; and Maastricht University, Maastricht, The Netherlands
FASEB J. 2015 Feb;29(2):374-84. doi: 10.1096/fj.13-243139. Epub 2014 Nov 3.
β1 integrins (β1) transduce mechanical signals in many cells, including cardiac myocytes (CM). Given their close localization, as well as their role in mechanotransduction and signaling, we hypothesized that caveolin (Cav) proteins might regulate integrins in the CM. β1 localization, complex formation, activation state, and signaling were analyzed using wild-type, Cav3 knockout, and Cav3 CM-specific transgenic heart and myocyte samples. Studies were performed under basal and mechanically loaded conditions. We found that: (1) β1 and Cav3 colocalize in CM and coimmunoprecipitate from CM protein lysates; (2) β1 is detected in a subset of caveolae; (3) loss of Cav3 caused reduction of β1D integrin isoform and active β1 integrin from the buoyant domains in the heart; (4) increased expression of myocyte Cav3 correlates with increased active β1 integrin in adult CM; (5) in vivo pressure overload of the wild-type heart results in increased activated integrin in buoyant membrane domains along with increased association between active integrin and Cav3; and (6) Cav3-deficient myocytes have perturbed basal and stretch mediated signaling responses. Thus, Cav3 protein can modify integrin function and mechanotransduction in the CM and intact heart.
β1 整合素（β1）在许多细胞中传递机械信号，包括心肌细胞（CM）。鉴于它们的紧密定位以及它们在机械转导和信号转导中的作用，我们假设窖蛋白（Cav）蛋白可能调节 CM 中的整合素。使用野生型、Cav3 敲除和 Cav3 CM 特异性转基因心脏和心肌细胞样本分析了β1 定位、复合物形成、激活状态和信号转导。在基础和机械加载条件下进行了研究。我们发现：（1）β1 和 Cav3 在 CM 中共定位，并从 CM 蛋白裂解物中共同免疫沉淀；（2）β1 检测到在一部分小窝中；（3）Cav3 的缺失导致心脏中浮力域中β1D 整合素同工型和活性β1 整合素减少；（4）心肌 Cav3 的表达增加与成年 CM 中活性β1 整合素的增加相关；（5）野生型心脏的体内压力超负荷导致浮力膜域中激活的整合素增加，同时活性整合素与 Cav3 之间的关联增加；（6）Cav3 缺陷型心肌细胞有扰乱的基础和拉伸介导的信号反应。因此，Cav3 蛋白可以修饰 CM 和完整心脏中的整合素功能和机械转导。
