CELL and I(3) Research Groups, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Department of Zoology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
CELL and I(3) Research Groups, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Neuroscience Research Group, Life Sciences Institute, Dept of Cellular and Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
FEBS Lett. 2014 Apr 17;588(8):1249-58. doi: 10.1016/j.febslet.2014.01.027. Epub 2014 Jan 28.
The gap junction family of proteins is widely expressed in mammalian cells and form intercellular channels between adjacent cells, as well as hemichannels, for transport of molecules between the cell and the surrounding environment. In addition, gap junction proteins have recently been implicated as important for the regulation of cell adhesion and migration in a variety of cell types. The gap junction protein connexin43 (Cx43) regulates B lymphocyte adhesion, BCR- and LFA-1-mediated activation of the GTPase Rap1, and cytoskeletal rearrangements resulting in changes to cell shape and membrane spreading. We demonstrate here that the actin cytoskeleton is important for the distribution of Cx43 in the B cell plasma membrane and for other cell processes involving the cytoskeleton. Using shRNA knockdown of Cx43 in B lymphoma cells we show that Cx43 is also necessary for chemokine-mediated Rap 1 activation, motility, CXCL12-directed migration, and movement across an endothelial cell monolayer. These results demonstrate that in addition to its role in B cell spreading, Cx43 is an important regulator of B-cell motility and migration, processes essential for normal B-cell development and immune responses.
缝隙连接蛋白家族广泛表达于哺乳动物细胞中，形成细胞间通道和半通道，以便在细胞与周围环境之间运输分子。此外，缝隙连接蛋白最近被认为对多种细胞类型的细胞黏附和迁移的调节很重要。缝隙连接蛋白连接蛋白 43（Cx43）调节 B 淋巴细胞黏附、BCR 和 LFA-1 介导的 GTPase Rap1 的激活，以及细胞骨架的重排导致细胞形状和膜铺展的变化。我们在这里证明，肌动蛋白细胞骨架对于 B 细胞质膜中 Cx43 的分布以及涉及细胞骨架的其他细胞过程很重要。使用 B 淋巴瘤细胞中的 shRNA 敲低 Cx43，我们表明 Cx43 对于趋化因子介导的 Rap1 激活、运动、CXCL12 定向迁移以及穿过内皮细胞单层的运动也是必需的。这些结果表明，除了在 B 细胞铺展中的作用外，Cx43 还是 B 细胞迁移和运动的重要调节剂，这些过程对于正常 B 细胞发育和免疫反应至关重要。
