An open gap junction, composed of six connexins.

Connexins, or gap junction proteins, are a family of structurally-related transmembrane proteins that assemble to form vertebrate gap junctions (an entirely different family of proteins, the innexins, form gap junctions in invertebrates).^[1] Each gap junction is composed of two hemichannels, or connexons, which are themselves each constructed out of six connexin molecules. Gap junctions are essential for many physiological processes, such as the coordinated depolarization of cardiac muscle, and proper embryonic development. For this reason, mutations in connexin-encoding genes can lead to functional and developmental abnormalities.

Structure

Nomenclature

In recent literature, connexins are most commonly named according to their molecular weights, e.g. Cx26 is the connexin protein of 26 kDa. This can lead to confusion however when connexin genes from different species are compared, e.g. human Cx36 is homologous to zebrafish Cx35. A competing nomenclature is the Gja/Gjb system, where connexins are sorted by their ? and ? forms, then assigned an identifying number, e.g. Gja1 corresponds to Cx43. The nomenclature of the connexin genes and proteins is currently under review by the HUGO Gene Nomenclature Committee.

Biosynthesis and Internalization

A remarkable aspect of connexins is that they have a relatively short half life of only a few hours.^[2] The result is the presence of a dynamic cycle by which connexins are synthesized and replaced. It has been suggested that this short life span allows for more finely regulated physiological processes to take place, such as in the myometrium.

From the Nucleus to the Membrane

As they are being translated by ribosomes, connexins are inserted into the membrane of the endoplasmic reticulum (ER) (Bennett and Zukin, 2004). It is in the ER that connexins are properly folded, yielding two extracellular loops, EL-1 and EL-2. It is also in the ER that the oligomerization of connexin molecules into hemichannels begins, a process which may continue in the UR-Golgi intermediate compartment as well.^[2] The arrangements of these hemichannels can be homotypic, heterotypic, and combined heterotypic/heteromeric.

After exiting the ER and passing through the ERGIC, the folded connexins will usually enter the cis-Golgi network.^[3] However, some connexins, such as Cx26 may be transported independent of the Golgi.^{[4][5][6][7][8]}

Gap Junction Assembly

After being inserted into the plasma membrane of the cell, the hemichannels freely diffuse within the lipid bilayer.^[9] Through the aid of specific proteins, mainly cadherins, the hemichannels are able to dock with hemichannels of adjacent cells forming gap junctions.^[10] Recent studies have shown the existence of communication between adherens junctions and gap junctions,^[11] suggesting a higher level of coordination than previously thought.

Function

Connexin gap junctions are found only in vertebrates. A functionally analogous but genetically unrelated group of proteins, the pannexins are expressed in both vertebrate and invertebrate species. The innexin proteins, invertebrate gap junction proteins, are probably pannexins. They have a similar structure, but don't share any sequence homology.

Within the CNS, gap junctions provide electrical coupling between progenitor cells, neurons, and glial cells. By using specific connexin KO mice, studies revealed that cell coupling is essential for visual signaling. In the retina, ambient light levels influence cell coupling provided by gap junction channels, adapting the visual function for various lighting conditions. Cell coupling is governed by several mechanisms, including connexin expression. ^[12]

Pathologies

List of Connexins

References

External links

ca:Connexina de:Connexin es:Conexina fi:Konneksiini

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