Márquez-Rosado Lucrecia, Solan Joell L, Dunn Clarence A, Norris Rachael P, Lampe Paul D
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Biochim Biophys Acta. 2012 Aug;1818(8):1985-92. doi: 10.1016/j.bbamem.2011.07.028. Epub 2011 Jul 26.
Gap junctions, composed of proteins from the connexin family, allow for intercellular communication between cells in essentially all tissues. There are 21 connexin genes in the human genome and different tissues express different connexin genes. Most connexins are known to be phosphoproteins. Phosphorylation can regulate connexin assembly into gap junctions, gap junction turnover and channel gating. Given the importance of gap junctions in development, proliferation and carcinogenesis, regulation of gap junction phosphorylation in response to wounding, hypoxia and other tissue insults is proving to be critical for cellular response and return to homeostasis. Connexin43 (Cx43) is the most widely and highly expressed gap junction protein, both in cell culture models and in humans, thus more research has been done on it and more reagents to it are available. In particular, antibodies that can report Cx43 phosphorylation status have been created allowing temporal examination of specific phosphorylation events in vivo. This review is focused on the use of these antibodies in tissue in situ, predominantly looking at Cx43 phosphorylation in brain, heart, endothelium and epithelium with reference to other connexins where data is available. These data allow us to begin to correlate specific phosphorylation events with changes in cell and tissue function. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.
间隙连接由连接蛋白家族的蛋白质组成,几乎在所有组织的细胞之间实现细胞间通讯。人类基因组中有21个连接蛋白基因,不同组织表达不同的连接蛋白基因。已知大多数连接蛋白是磷蛋白。磷酸化可调节连接蛋白组装成间隙连接、间隙连接的更新以及通道门控。鉴于间隙连接在发育、增殖和致癌作用中的重要性,事实证明,响应伤口、缺氧和其他组织损伤而对间隙连接磷酸化进行调节对于细胞反应和恢复内环境稳态至关重要。连接蛋白43(Cx43)是在细胞培养模型和人类中表达最广泛且表达量最高的间隙连接蛋白,因此对其开展的研究更多,可用的试剂也更多。特别是,已经制备了能够报告Cx43磷酸化状态的抗体,从而可以对体内特定的磷酸化事件进行实时检测。本综述重点关注这些抗体在组织原位的应用,主要研究脑、心脏、内皮和上皮中的Cx43磷酸化,并参考其他有数据的连接蛋白。这些数据使我们能够开始将特定的磷酸化事件与细胞和组织功能的变化联系起来。本文是名为《通讯连接、组成、结构和特性》特刊的一部分。