Innexin

Innexin
Identifiers
Symbol Innexin
Pfam PF00876
InterPro IPR000990
TCDB 1.A.25

Innexins are transmembrane proteins that form gap junctions in invertebrates. Gap junctions are composed of membrane proteins that form a channel permeable to ions and small molecules connecting the cytoplasm 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 the connexin family of gap junction proteins was well-characterized in vertebrates, no homologues were found in non-chordates.

Discovery

Gap junction proteins with no sequence homology to connexins were initially identified in fruit flies. It was suggested that these proteins are specific invertebrate gap junctions, and they were thus named "innexins" (invertebrate analog of connexins).[1] 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 Greek pan - all, throughout, and Latin nexus - connection, bond).[2][3] However, increasing evidence suggests that pannexons do not form gap junctions unless overexpressed in tissue and thus, differ functionally from innexins.[4]

Structure

Innexins have four transmembrane segments (TMSs) and, like the vertebrate connexin gap junction protein, six innexin subunits together form a channel (an "innexon") in the plasma membrane of the cell.[5] Two innexons in apposed plasma membranes can form a gap junction. Structurally, pannexins are similar to connexins. Both types of protein consist of a cytoplasmic N-terminal domain, followed by four (TMSs) that delimit one cytoplasmic and two extracellular loops; the C- terminal domain is cytoplasmic. In addition, pannexin1 and pannexin2 channels show quaternary similarities to connexons, but different oligomerization numbers.[6]

Vinnexins, viral homologues of innexins, were identified in polydnaviruses 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.[7][8]

Function

Pannexins can form nonjunctional transmembrane “hemichannels” for transport of molecules of less than 1000 Da, or intercellular gap junctions. 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.[9] Pannexin 1 constitutes the large conductance cation channel of cardiac myocytes.[10] Pannexin 1 and pannexin 2 underlie channel function in neurons and contribute to ischemic brain damage.[11]

In addition to making gap junctions, innexins also form non-junctional membrane channels with properties similar to those of pannexons.[12] N-terminal- elongated innexins can act as a plug to manipulate hemichannel closure and provide a mechanism connecting the effect of hemichannel closure directly to apoptotic signal transduction from the intracellular to the extracellular compartment.[13]

Transport reaction

The transport reactions catalyzed by innexin gap junctions is:

Small molecules (cell 1 cytoplasm) ⇌ small molecules (cell 2 cytoplasm)

Or for hemichannels:

Small molecules (cell cytoplasm) ⇌ small molecules (out)

Examples

See also

References

  1. ↑ Phelan P, Stebbings LA, Baines RA, Bacon JP, Davies JA, Ford C (1998). "Drosophila Shaking-B protein forms gap junctions in paired Xenopus oocytes". Nature. 391 (6663): 181–184. doi:10.1038/34426. PMID 9428764.
  2. ↑ Lukyanov S, Usman N, Panchin Y, Kelmanson I, Matz M, Lukyanov K (2000). "A ubiquitous family of putative gap junction molecules". Curr. Biol. 10 (13): –. doi:10.1016/S0960-9822(00)00576-5. PMID 10898987.
  3. ↑ Matz MV, Lukyanov SA, Kelmanson IV, Shagin DA, Usman N, Panchin YV (2002). "Altering electrical connections in the nervous system of the pteropod mollusc Clione limacina by neuronal injections of gap junction mRNA". Eur. J. Neurosci. 16 (12): 2475–2476. doi:10.1046/j.1460-9568.2002.02423.x. PMID 12492443.
  4. ↑ Dahl G. & Harris A. 2009. Pannexins or Connexins? Chapter 12. In: A. Harris, D. Locke (eds.), Connexins: A Guide doi:10.1007/978-1-59745-489-6_12
  5. ↑ Bao, L.; Samuels, S.; Locovei, S.; MacAgno, E.; Muller, K.; Dahl, G. (2007). "Innexins Form Two Types of Channels". FEBS Letters. 581 (29): 5703–5708. doi:10.1016/j.febslet.2007.11.030. PMC 2489203Freely accessible. PMID 18035059.
  6. ↑ Ambrosi, Cinzia; Gassmann, Oliver; Pranskevich, Jennifer N.; Boassa, Daniela; Smock, Amy; Wang, Junjie; Dahl, Gerhard; Steinem, Claudia; Sosinsky, Gina E. (2010-08-06). "Pannexin1 and Pannexin2 channels show quaternary similarities to connexons and different oligomerization numbers from each other". The Journal of Biological Chemistry. 285 (32): 24420–24431. doi:10.1074/jbc.M110.115444. ISSN 1083-351X. PMC 2915678Freely accessible. PMID 20516070.
  7. ↑ Turnbull M, Webb B (2002). "Perspectives on polydnavirus origins and evolution". Adv. Virus Res. 58: 203–254. doi:10.1016/S0065-3527(02)58006-4. PMID 12205780.
  8. ↑ Kroemer JA, Webb BA (2004). "Polydnavirus genes and genomes: emerging gene families and new insights into polydnavirus replication". Annu Rev Entomol. 49 (1): 431–456. doi:10.1146/annurev.ento.49.072103.120132. PMID 14651471.
  9. ↑ Shestopalov, V. I.; Panchin, Y. (2008-02-01). "Pannexins and gap junction protein diversity". Cellular and molecular life sciences: CMLS. 65 (3): 376–394. doi:10.1007/s00018-007-7200-1. ISSN 1420-682X. PMID 17982731.
  10. ↑ Limaye, S. R.; Mahmood, M. A. (1987-10-01). "Retinal microangiopathy in pigmented paravenous chorioretinal atrophy.". The British Journal of Ophthalmology. 71 (10): 757–761. ISSN 0007-1161. PMC 1041301Freely accessible. PMID 3676145.
  11. ↑ Bargiotas, Panagiotis; Krenz, Antje; Hormuzdi, Sheriar G.; Ridder, Dirk A.; Herb, Anne; Barakat, Waleed; Penuela, Silvia; von Engelhardt, Jakob; Monyer, Hannah (2011-12-20). "Pannexins in ischemia-induced neurodegeneration". Proceedings of the National Academy of Sciences of the United States of America. 108 (51): 20772–20777. doi:10.1073/pnas.1018262108. ISSN 1091-6490. PMC 3251101Freely accessible. PMID 22147915.
  12. ↑ Bao, Li; Samuels, Stuart; Locovei, Silviu; Macagno, Eduardo R.; Muller, Kenneth J.; Dahl, Gerhard (2007-12-11). "Innexins form two types of channels". FEBS letters. 581 (29): 5703–5708. doi:10.1016/j.febslet.2007.11.030. ISSN 0014-5793. PMC 2489203Freely accessible. PMID 18035059.
  13. ↑ Chen, Ya-Bin; Xiao, Wei; Li, Ming; Zhang, Yan; Yang, Yang; Hu, Jian-Sheng; Luo, Kai-Jun (2016-05-01). "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. ISSN 1520-6327. PMID 27030553.

Further reading

External links

This article incorporates text from the public domain Pfam and InterPro IPR000990

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