Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, USA.
Physiology (Bethesda). 2013 Mar;28(2):93-116. doi: 10.1152/physiol.00038.2012.
Gap junctions (GJs) are the only known cellular structures that allow a direct cell-to-cell transfer of signaling molecules by forming densely packed arrays or "plaques" of hydrophilic channels that bridge the apposing membranes of neighboring cells. The crucial role of GJ-mediated intercellular communication (GJIC) for all aspects of multicellular life, including coordination of development, tissue function, and cell homeostasis, has been well documented. Assembly and degradation of these membrane channels is a complex process that includes biosynthesis of the connexin (Cx) subunit proteins (innexins in invertebrates) on endoplasmic reticulum (ER) membranes, oligomerization of compatible subunits into hexameric hemichannels (connexons), delivery of the connexons to the plasma membrane (PM), head-on docking of compatible connexons in the extracellular space at distinct locations, arrangement of channels into dynamic spatially and temporally organized GJ channel plaques, as well as internalization of GJs into the cytoplasm followed by their degradation. Clearly, precise modulation of GJIC, biosynthesis, and degradation are crucial for accurate function, and much research currently addresses how these fundamental processes are regulated. Here, we review posttranslational protein modifications (e.g., phosphorylation and ubiquitination) and the binding of protein partners (e.g., the scaffolding protein ZO-1) known to regulate GJ biosynthesis, internalization, and degradation. We also look closely at the atomic resolution structure of a GJ channel, since the structure harbors vital cues relevant to GJ biosynthesis and turnover.
间隙连接（GJ）是唯一已知的允许通过形成密集排列的亲水性通道“斑块”或“斑块”将信号分子直接从一个细胞转移到另一个细胞的细胞结构，这些通道桥接相邻细胞的对应膜。GJ 介导的细胞间通讯（GJIC）在多细胞生命的所有方面都起着至关重要的作用，包括协调发育、组织功能和细胞内稳态，这一点已经得到了很好的证明。这些膜通道的组装和降解是一个复杂的过程，包括连接蛋白（Cx）亚基蛋白（无脊椎动物中的连接蛋白）在内质网（ER）膜上的生物合成、相容亚基的寡聚化形成六聚体半通道（连接子）、将连接子递送到质膜（PM）、在不同位置的细胞外空间对头对头对接相容的连接子、将通道排列成动态的空间和时间组织的 GJ 通道斑块，以及 GJ 内化到细胞质中随后降解。显然，GJIC、生物合成和降解的精确调节对于准确的功能至关重要，目前许多研究都致力于研究这些基本过程是如何被调节的。在这里，我们回顾了已知调节 GJ 生物合成、内化和降解的翻译后蛋白修饰（如磷酸化和泛素化）和蛋白伴侣（如支架蛋白 ZO-1）的结合。我们还仔细研究了 GJ 通道的原子分辨率结构，因为该结构包含与 GJ 生物合成和周转相关的重要线索。
