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Gap junctions are composed of two hemichannels, and each of them has six membrane spanning proteins. These proteins are called connexins (Cx) in mammals, and innexins (Inx) in invertebrates. Recently innexine-like sequencies have also been found in mammals. They have been referred to as pannexins (Panx).

Gap junctions are found in essentially all tissues at some stage of development suggesting that they could have much more functions besides electrical signaling in neurons.

Types of innexins

First discovered gap junction proteins were innexins in crayfish [1]. They were originally identified as structural proteins of gap junctions in the Drosophila and the C. Elegans [2]. Later Inx were found in Arthropoda (Drosophila, grasshopper), Nematoda (C. Elegans), Annelida (Medicinal leech), Platyhelminthes (flatworm) and Mollusca phylum. Homologous proteins were found even in Hydra and insect viruses. The Ichnovirus proteins are closely related to the insect innnexins (similarity of approximately 50%).

So far well over 50 innexin sequences have been found. The Drosophila has 8, and the C. Elegans 25, Inx genes [3]. Some of Drosophila innexins are called ogre, shak-B, inx2, inx3, inx4 and are responsible for synaptic transmission, for epithelial morphogenesis, for survival of differentiating germ cells and other purposes [4].

Innexin Structure

Even if connexins and innexines/ pannexins have no sequence homology, they share the same topology. Both types of protein have two extracellular and one cytoplasmic loop with intracellular N- and C- termini. Many of the innexins have introns in their coding regions, differently from connexins. Thus innexins have the potential to produce more than one protein from one gene by differential splicing.

Many cell types express multiple Cx, Inx or Panx proteins. This allows to make homooligomeric (they have the same proteins) and heterooligomeric (they have different proteins) hemichannels. These, in turn, can assemble into homotypic (consist of two identical) and heterotypic (consist of two different) gap junction channels. This creates the wide variety of possible gap junction combinations. A number of proteins, for example, Drosophila Inx3, Cx33 and Panx2, do not seem to form homomeric channels [4]. These may influence the formation and properties of channels built of other proteins. The physiological significance of heterotypic hemichannels is not known but it could provide a means of coupling different cell types.


Traditionally Inx role was thought to be only for making gap junctions. Now Inx are known to have more function. Since most research has been done in Drosophila and C. Elegans, most of the functions are described for these organisms. Mutations in Drosophila and C. Elegans Inx genes (shak-B and unc-7/ unc-9, respectively) interfere with behavior, these mutants have uncoordinated phenotype. It was found that Inx synchronize muscle contraction, are required for survival of differentiating germ cells, postembryonic development, epithelial morphogenesis, cell proliferation and other purposes [4].

Alternatively, Inx may serve a role as hemichannels. Although hemichannels present in the non-junctional regions of the plasma membrane are believed to be kept closed, some cells can keep them opened. It might exert some physiological or deleterious effects.


1. E.J. Furshpan, D.D. Potter, (1959). Transmission at the giant motor synapses of the crayfish, J. Physiol., 145: 289– 325.

2. P. Phelan, J.P. Bacon, J.A. Davies, L.A. Stebbings, M.G. Todman, L. Avery, R.A. Baines, T.M. Barnes, C. Ford, S. Hekimi, R. Lee, J.E. Shaw, T.A. Starich, K.D. Curtin, Y.-A. Sun, R.J. Wyman, (1998). Innexins: a family of invertebrate gap-junction proteins. Trends Genet., 14: 348–349.

3. P. Phelan, T.A. Starich, Innexins get into the gap, (2001). BioEssays, 23: 388– 396.

4. Phelan P. (2005). Innexins: members of an evolutionarily conserved family of gap-junction proteins. Biochim Biophys Acta., 1711(2):225-245.