Baker Susan M, Kim Namho, Gumpert Anna M, Segretain Dominique, Falk Matthias M
Department of Biological Sciences, Lehigh University, 111 Research Drive, Iacocca Hall, Bethlehem, PA 18015, USA.
FEBS Lett. 2008 Dec 10;582(29):4039-46. doi: 10.1016/j.febslet.2008.10.043. Epub 2008 Nov 4.
During the inflammatory response, activation of G-protein coupled receptors (GPCRs) by inflammatory mediators rapidly leads to inhibition of gap junction intercellular communication (GJIC); however, the steps that lead to this inhibition are not known. Combining high-resolution fluorescence microscopy and functional assays, we found that activation of the GPCRs PAR-1 and ET(A/B) by their natural inflammatory mediator agonists, thrombin and endothelin-1, resulted in rapid and acute internalization of gap junctions (GJs) that coincided with the inhibition of GJIC followed by increased vascular permeability. The endocytosis protein clathrin and the scaffold protein ZO-1 appeared to be involved in GJ internalization, and ZO-1 was partially displaced from GJs during the internalization process. These findings demonstrate that GJ internalization is an efficient mechanism for modulating GJIC in inflammatory response.
在炎症反应过程中，炎症介质激活G蛋白偶联受体（GPCRs）会迅速导致间隙连接细胞间通讯（GJIC）受到抑制；然而，导致这种抑制的具体步骤尚不清楚。结合高分辨率荧光显微镜和功能测定，我们发现GPCRs PAR-1和ET(A/B)被其天然炎症介质激动剂凝血酶和内皮素-1激活后，会导致间隙连接（GJs）迅速急性内化，这与GJIC的抑制同时发生，随后血管通透性增加。内吞蛋白网格蛋白和支架蛋白ZO-1似乎参与了GJ内化，并且在内化过程中ZO-1会从GJs上部分移位。这些发现表明，GJ内化是炎症反应中调节GJIC的一种有效机制。
