Investigation of pannexins - ubiquitous family of putative gap junction molecules

Shagin D, Bogdanova E, Zhulidov P, Wagner L, Shcheglov A.
(in collaboration with Dr. Panchin Y. And Dr. Kelmanson I., A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University
AND Vavilov Institute of General Genetics RAS, Gubkina str., 3 GSP-1, Moscow 119991, Russia.)

Gap junctions are one of the most common forms of intercellular communication. They are composed of membrane proteins that form a channel permeable for ions and small molecules connecting the cytoplasm of adjacent cells. Although gap junctions provide similar functions in all multicellular organisms, vertebrates and invertebrates are believed to use unrelated proteins for this purpose. The family of gap junction molecules called connexins is well-characterized in vertebrates, but no homologs of these proteins have been found in invertebrates. In turn, only gap junction molecules with no sequence homology to connexins have been identified so far in insects and nematodes. It was suggested that these are specific invertebrate gap junction proteins, and they were thus named innexins (invertebrate analog of connexins).
We have cloned sequences homologues to innexins from mollusk and flatworm cDNA. This finding is important because it refutes the hypothesis that innexins could represent a specific feature of "moulting animals" that include among others arthropods and nematodes but not mollusks and flatworms. We demonstrated that intracellular injection of mRNA encoding the molluscan innexin Panx1 drastically alters the specificity of electrical coupling between identified neurons of the pteropod mollusc Clione limacine.
Moreover, we cloned the genes PANX1, PANX2 and PANX3, encoding homologous to invertebrate innexins, which constitute a new family of mammalian proteins. Thus, the list of animal phyla with identified innexin family members extends to Platyhelminthes, Nematoda, Arthropoda, Mollusca and even Chordata, which makes the 'innexin' name inappropriate. Given the apparent ubiquitous distribution of this protein family in the animal kingdom we suggest that they should be called pannexins (from the Latin pan - all, throughout and nexus - connection, bond).
Phylogenetic analysis revealed that pannexins are highly conserved in worms, mollusks, insects and mammals, pointing to their important function. Pannexins (including innexins) are predicted to have four transmembrane regions, two extracellular loops, one intracellular loop and intracellular N and C termini. Both the human and mouse genomes contain three pannexin-encoding genes. The human and mouse pannexin-1 mRNAs are ubiquitously, although disproportionately, expressed in normal tissues. Human PANX2 is a brain-specific gene; its mouse orthologue, Panx2, is also expressed in certain cell types in developing brain. In silico evaluation of Panx3 expression predicts gene expression in osteoblasts and synovial fibroblasts. The apparent conservation of pannexins between species merits further investigation.