Is the junctional uncoupling elicited in rat ventricular myocytes by some dephosphorylation treatments due to changes in the phosphorylation status of Cx43?
Is the junctional uncoupling elicited in rat ventricular myocytes by some dephosphorylation treatments due to changes in the phosphorylation status of Cx43?
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DOI：
10.1007/s00249-003-0381-0
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发表时间：
2004-05-01
影响因子：
2
通讯作者：
Sarrouilhe, D
中科院分区：
文献类型：
--
作者：
Hervé, JC;Plaisance, I;Sarrouilhe, D
缝隙连接是一种特殊的膜结构，在几乎所有的动物组织中介导细胞与细胞之间的通讯，它是由称为连接蛋白的通道形成膜蛋白组成的。它们中的大多数，特别是连接蛋白43（Cx43），最普遍的连接蛋白，心肌细胞中存在的主要连接蛋白，是磷蛋白。连接蛋白磷酸化被认为调节间隙连接蛋白跟踪、间隙连接组装、通道门控和周转。当细胞暴露于磷酸化或去磷酸化处理时，一些连接蛋白，包括Cx43，在凝胶电泳中显示迁移率变化。然而，大鼠心肌细胞暴露于不同的解偶联去磷酸化剂，如H7或丁二酮单肟，没有modi。Cx43磷酸化蛋白中的阳离子。一般都是观察。细胞间通讯的抑制与Cx43磷酸化模式的变化或相反，与modi.阳离子的后者没有修改。阳离子的细胞间耦合程度，表明连接通道的功能状态，而可能是由与Cx43相关的调节蛋白。通过蛋白质磷酸化/去磷酸化过程调节连接通道的活性很可能需要（对于其他几种膜通道）形成多蛋白复合物，其中孔形成亚基与辅助蛋白结合（例如，G.支架蛋白、酶、细胞骨架元件）在通道定位和活性中起重要作用。这种调节蛋白，作为磷酸化/去磷酸化催化剂的目标，可能特别控制连接通道的开放概率。提出了一个示意图的调节Cx43的通道蛋白磷酸化涉及的合作伙伴磷蛋白。
Gap junctions, specialized membrane structures that mediate cell- to- cell communication in almost all animal tissues, are composed of channel- forming integral membrane proteins termed connexins. Most of them, particularly connexin43 ( Cx43), the most ubiquitous connexin, the major connexin present in cardiac myocytes, are phosphoproteins. Connexin phosphorylation has been thought to regulate gap junctional protein tracking, gap junction assembly, channel gating, and turnover. Some connexins, including Cx43, show mobility shifts in gel electrophoresis when cells are exposed to phosphorylating or dephosphorylating treatments. However, after exposure of rat cardiac myocytes to different uncoupling dephosphorylating agents such as H7 or butanedione monoxime, no modi. cation in the Cx43 phosphorylation pro. le was generally observed. The lack of direct correlation between the inhibition of cell- to- cell communication and changes in the phosphorylation pattern of Cx43 or, conversely, modi. cations of the latter without modi. cations of the intercellular coupling degree, suggest that the functional state of junctional channels might rather be determined by regulatory proteins associated with Cx43. The modulation of the activity of junctional channels by protein phosphorylation/ dephosphorylation processes very likely requires ( as for several other membrane channels) the formation of a multiprotein complex, where poreforming subunits bind to auxiliary proteins ( e. g. scaffolding proteins, enzymes, cytoskeleton elements) that play essential roles in channel localization and activity. Such regulatory proteins, behaving as targets for phosphorylation/ dephosphorylation catalysers, might in particular control the open probability of junctional channels. A schematic illustration of the regulation of Cx43- made channels by protein phosphorylation involving a partner phosphoprotein is proposed.