ギャップ結合チャネルの構造と多様性

Abstract

Most multicellular organisms possess gap junctions that mediate cell–cell communication. Gap junctions form a 2~4 nm gap between adjacent cells, and include a cluster of multiple channels, each of which is referred to as a gap junction channel. Gap junction channels comprise oligomers of four transmembrane proteins, and allow for the passage of small signal molecules (~a few thousand Dalton) through the central conduit. Interestingly, two gene families with a common function have evolved. Connexins form a family encoding genes for gap junctions expressed in chordates, including vertebrates. Innexins were originally identified in Drosophila and Caenorhabditis elegans, and form a family of invertebrate gap junction channels. The gene members of these two families do not exhibit any homology in terms of their amino acid sequences, and are thus thought to be evolutionary independent, but the electron micrographs of these two families of channels appear very similar. Structural studies of connexin channels in association with inherited human diseases identified that one connexin gap junction channel comprises 12 subunits. Few studies have examined the structural properties of innexin channels, however, and they remain poorly understood. This review discusses the three–dimensional structure of connexin channels, as well as recent advances in our understanding of innexin structures, whose structure appears to differ from that of connexin.