The vertebrate connexin family

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The vertebrate connexin family. V. Cruciani and S.-O. Mikalsen*. Institute for Cancer Research, The Norwegian Radium Hospital, 0310 Oslo (Norway), Fax: + 47 ...
Cell. Mol. Life Sci. 63 (2006) 1125–1140 1420-682X/06/101125-16 DOI 10.1007/s00018-005-5571-8 © Birkhäuser Verlag, Basel, 2006

Cellular and Molecular Life Sciences

Review The vertebrate connexin family V. Cruciani and S.-O. Mikalsen* Institute for Cancer Research, The Norwegian Radium Hospital, 0310 Oslo (Norway), Fax: + 47 22935767, e-mail: [email protected] Received 1 December 2005; received after revision 8 January 2005; accepted 31 January 2006 Online First 29 March 2006 Abstract. Connexins are chordate-specific transmembrane proteins that can form gap junctional channels between adjacent cells. With the progress in vertebrate genome sequencing, it is now possible to reconstruct the main lines in the evolution of the connexin family from fishes to mammals. Four connexin groups are only found in fishes. Otherwise, the differences between fishes and mammals can be explained by two gene losses (Cx39.9 and Cx43.4) after the divergence of the Reptilia, and three

gene duplications (the generation of Cx26 and 30 from a preCx26/30 sequence, Cx30.3 and 31.1 from a preCx30.3/ 31.1 sequence, and Cx31.3 from an uncertain origin). Orthologs of most connexins can be found throughout the vertebrates from fishes to mammals. As judged from the recently defined connexins in tunicates, the original connexin might be related to the ortholog groups of Cx36, 39.2, 43.4, 45 or 47.

Keywords. Gap junction, pannexin, connexin, evolution, phylogeny, synteny, chromosome.

Introduction Gap junction plaques are clusters of transmembrane channels that allow direct contact between the cytoplasm of one cell and the cytoplasm of its neighbor. Each cell participates with one hemichannel. In vertebrates, the hemichannel is called a connexon, and each connexon is made of six protein subunits named connexins. Due to these junctions, all the cells in a communicating tissue potentially share a pool of small molecules (