Guo Yuanjian, Yang Lu, Haught Katrina, Scarlata Suzanne
From the Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York 11794-8661.
From the Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York 11794-8661
J Biol Chem. 2015 Jul 3;290(27):16698-707. doi: 10.1074/jbc.M115.655126. Epub 2015 May 8.
Caveolae are membrane invaginations that can sequester various signaling proteins. Caveolae have been shown to provide mechanical strength to cells by flattening to accommodate increased volume when cells are subjected to hypo-osmotic stress. We have previously found that caveolin, the main structural component of caveolae, specifically binds Gαq and stabilizes its activation state resulting in an enhanced Ca(2+) signal upon activation. Here, we show that osmotic stress caused by decreasing the osmolarity in half reversibly changes the configuration of caveolae without releasing a significant portion of caveolin molecules. This change in configuration due to flattening leads to a loss in Cav1-Gαq association. This loss in Gαq/Cav1 association due to osmotic stress results in a significant reduction of Gαq/phospholipase Cβ-mediated Ca(2+) signals. This reduced Ca(2+) response is also seen when caveolae are reduced by treatment with siRNA(Cav1) or by dissolving them by methyl-β-cyclodextran. No change in Ca(2+) release with osmotic swelling can be seen when growth factor pathways are activated. Taken together, these results connect the mechanical deformation of caveolae to Gαq-mediated Ca(2+) signals.
小窝是能够隔离各种信号蛋白的膜内陷结构。研究表明，当细胞受到低渗应激时，小窝会通过变平以容纳增加的体积，从而为细胞提供机械强度。我们之前发现，小窝的主要结构成分小窝蛋白特异性结合Gαq并稳定其激活状态，从而在激活时增强Ca(2+)信号。在此，我们表明，将渗透压减半所引起的渗透应激会可逆地改变小窝的结构，而不会释放大部分小窝蛋白分子。这种因变平导致的结构变化会导致Cav1 - Gαq结合的丧失。由于渗透应激导致的Gαq/Cav1结合丧失会导致Gαq/磷脂酶Cβ介导的Ca(2+)信号显著减少。在用siRNA(Cav1)处理或用甲基-β-环糊精溶解小窝从而减少小窝时，也会出现这种Ca(2+)反应降低的情况。当生长因子途径被激活时，渗透压肿胀引起的Ca(2+)释放没有变化。综上所述，这些结果将小窝的机械变形与Gαq介导的Ca(2+)信号联系起来。
