Innexins aretransmembrane proteins that formgap junctions ininvertebrates. Gap junctions are composed ofmembrane proteins that form achannel permeable to ions and small molecules connecting thecytoplasm of adjacent cells. Although gap junctions provide similar functions in all multicellular organisms, it was not known what proteins invertebrates used for this purpose until the late 1990s. While theconnexin family of gap junction proteins was well-characterized invertebrates, no homologues were found innon-chordates.
Innexins or related proteins are widespread amongEumetazoa, with the exception ofechinoderms.[1]
Gap junction proteins with nosequence homology to connexins were initially identified infruit flies. It was suggested that these proteins are specific invertebrate gap junctions, and they were thus named "innexins" (invertebrate analog of connexins).[2] They were later identified in diverse invertebrates. Invertebrate genomes may contain more than a dozen innexin genes. Once the human genome was sequenced, innexin homologues were identified in humans and then in other vertebrates, indicating their ubiquitous distribution in the animal kingdom. These homologues were called "pannexins" (from the Greekpan - all, throughout, and Latinnexus - connection, bond).[3][4] However, increasing evidence suggests that pannexins do not form gap junctions unless overexpressed in tissue and thus, differ functionally from innexins.[5]
Innexins have fourtransmembrane segments (TMSs) and, like the vertebrateconnexin gap junction protein, innexin subunits together form a channel (an "innexon") in theplasma membrane of the cell.[6] Two innexons in apposed plasma membranes can form a gap junction. Innexons are made from eight subunits, instead of the six subunits of connexons.[7] Structurally, innexins and connexins are very similar, consisting of 4 transmembrane domains, 2 extracellular and 1 intracellular loop, along with intracellular N- and C-terminal tails. Despite this shared topology, the protein families do not share enough sequence similarity to confidently infer common ancestry.
Pannexins are similar to innexins and are usually considered a sub-group, but they do not participate in the formation of gap junctions and the channels have seven subunits.[8][9]
Vinnexins, viral homologues of innexins, were identified inpolydnaviruses that occur in obligate symbiotic associations with parasitoid wasps. It was suggested that vinnexins may function to alter gap junction proteins in infected host cells, possibly modifying cell-cell communication during encapsulation responses in parasitized insects.[10][11][12]
Innexins form gap junctions found in invertebrates. They also form non-junctional membrane channels with properties similar to those of pannexons.[13] N-terminal- elongated innexins can act as a plug to manipulate hemichannel closure and provide a mechanism connecting the effect of hemichannel closure directly toapoptoticsignal transduction from the intracellular to the extracellular compartment.[14]
The vertebrate homolog pannexin do not form gap junctions. They only form the hemichannel "pannexons". These hemichannels can be present in plasma, ER and Golgi membranes. They transport Ca2+, ATP,inositol triphosphate and other small molecules and can form hemichannels with greater ease than connexin subunits.[15]
^Kelmanson IV, Shagin DA, Usman N, Matz MV, Lukyanov SA, Panchin YV (December 2002). "Altering electrical connections in the nervous system of the pteropod mollusc Clione limacina by neuronal injections of gap junction mRNA".The European Journal of Neuroscience.16 (12):2475–6.doi:10.1046/j.1460-9568.2002.02423.x.PMID12492443.S2CID41324492.
^Dahl G. & Harris A. 2009. Pannexins or Connexins? Chapter 12. In: A. Harris, D. Locke (eds.), Connexins: A Guidedoi:10.1007/978-1-59745-489-6_12
^Kroemer JA, Webb BA (2004). "Polydnavirus genes and genomes: emerging gene families and new insights into polydnavirus replication".Annual Review of Entomology.49 (1):431–56.doi:10.1146/annurev.ento.49.072103.120132.PMID14651471.
^Chen YB, Xiao W, Li M, Zhang Y, Yang Y, Hu JS, Luo KJ (May 2016). "N-TERMINALLY ELONGATED SpliInx2 AND SpliInx3 REDUCE BACULOVIRUS-TRIGGERED APOPTOSIS VIA HEMICHANNEL CLOSURE".Archives of Insect Biochemistry and Physiology.92 (1):24–37.doi:10.1002/arch.21328.PMID27030553.
Dykes IM, Macagno ER (April 2006). "Molecular characterization and embryonic expression of innexins in the leech Hirudo medicinalis".Development Genes and Evolution.216 (4):185–97.doi:10.1007/s00427-005-0048-1.PMID16440200.S2CID21780341.
