Editing Gap junction (section)

==Structure==
[[File:Camillo Peracchia fig4-6.png|thumb|left|Connexon pairing across membranes bridges the gap between two cells and between vesicles to membranes.<ref name="globules">{{cite journal |last1=Peracchia |first1=Camillo |title=Low Resistance Junctions in Crayfish |journal=Journal of Cell Biology |date=1 April 1973 |volume=57 |issue=1 |pages=66–76 |doi=10.1083/jcb.57.1.66|pmid=4120611 |pmc=2108946 }}</ref>]]In [[vertebrate]]s, gap junction [[hemichannel]]s are primarily homo- or hetero-[[hexamer]]s of [[connexin]] [[protein]]s. Hetero-hexamers at gap junction plaques, help form a uniform intercellular space of 2-4&nbsp;nm.<ref name="maeda">{{Cite journal|pmid=19340074 |year=2009 |first1=Shoji |last1=Maeda |first2=So |last2=Nakagawa |first3=Michihiro |last3=Suga |first4=Eiki |last4=Yamashita |first5=Atsunori |last5=Oshima |first6=Yoshinori |last6=Fujiyoshi |first7=Tomitake |last7=Tsukihara |title=Structure of the connexin 26 gap junction channel at 3.5 A resolution |volume=458 |issue=7238 |pages=597–602 |doi=10.1038/nature07869 |journal=Nature|bibcode = 2009Natur.458..597M |s2cid=4431769 }}</ref> In this way hemichannels in the membrane of each cell are aligned with one another forming an [[intercellular communication]] path.<ref>{{Cite journal|pmid=9514740 |year=1998 |first1=Guy A. |last1=Perkins |first2=Daniel A. |last2=Goodenough |first3=Gina E. |last3=Sosinsky |title=Formation of the gap junction intercellular channel requires a 30 degree rotation for interdigitating two apposing connexons |volume=277 |issue=2 |pages=171–7 |journal=Journal of Molecular Biology |doi=10.1006/jmbi.1997.1580}}</ref>

[[Invertebrate]] gap junctions comprise [[protein]]s from the [[innexin]] [[protein family|family]]. Innexins have no significant sequence [[Homology (biology)|homology]] with connexins.<ref>{{cite journal|author=The C. elegans Sequencing Consortium |title=Genome sequence of the nematode C. elegans: a platform for investigating biology|journal=Science |date=Dec 11, 1998|volume=282|issue=5396|pages=2012–2018|pmid=9851916|doi=10.1126/science.282.5396.2012 |bibcode=1998Sci...282.2012.}}</ref> Though differing in sequence to connexins, innexins are similar enough to connexins to form gap junctions ''in vivo'' in the same way connexins do.<ref>{{cite journal|last1=Ganfornina|first1=MD|last2=Sánchez|first2=D|last3=Herrera |first3=M|last4=Bastiani|first4=MJ|title=Developmental expression and molecular characterization of two gap junction channel proteins expressed during embryogenesis in the grasshopper Schistocerca americana |journal=Developmental Genetics|date=1999|volume=24|issue=1–2|pages=137–150|pmid=10079517 |doi=10.1002/(SICI)1520-6408(1999)24:1/2<137::AID-DVG13>3.0.CO;2-7|hdl=10261/122956}}</ref><ref>{{cite journal|last1=Starich|first1=T. A.|title=eat-5 and unc-7 represent a multigene family in Caenorhabditis elegans involved in cell-cell coupling|journal=J. Cell Biol.|date=1996|volume=134|issue=2|pages=537–548|pmc=2120886|doi=10.1083/jcb.134.2.537 |pmid=8707836}}</ref><ref>{{cite journal|last1=Simonsen |first1=Karina T.|last2=Moerman|first2=Donald G.|last3=Naus|first3=Christian C.|title=Gap junctions in C. elegans|journal=Frontiers in Physiology|volume=5|pages=40 |doi=10.3389/fphys.2014.00040|pmid=24575048 |pmc=3920094|year=2014|doi-access=free}}</ref>

The more recently characterized [[pannexin]] family,<ref>{{cite journal|last1=Barbe|first1=M. T.|title=Cell-Cell Communication Beyond Connexins: The Pannexin Channels|journal=Physiology|date=1 April 2006|volume=21|issue=2|pages=103–114|pmid=16565476 |doi=10.1152/physiol.00048.2005}}</ref> which was originally thought to form intercellular channels (with an [[amino acid]] sequence similar to innexins<ref>{{cite journal|last1=Panchina|first1=Yuri |last2=Kelmanson|first2=Ilya|last3=Matz|first3=Mikhail|last4=Lukyanov|first4=Konstantin|last5=Usman |first5=Natalia|last6=Lukyanov |first6=Sergey|title=A ubiquitous family of putative gap junction molecules|journal=Current Biology|volume=10|issue=13|pages=R473–R474|doi=10.1016/S0960-9822(00)00576-5|pmid=10898987|date=June 2000|s2cid=20001454|doi-access=free|bibcode=2000CBio...10.R473P }}</ref>) in fact functions as a single-membrane channel that communicates with the extracellular environment and has been shown to pass calcium and [[Adenosine triphosphate|ATP]].<ref>{{cite journal|last1=Lohman |first1=Alexander W. |last2=Isakson|first2=Brant E.|title=Differentiating connexin hemichannels and pannexin channels in cellular ATP release|journal=FEBS Letters|volume=588|issue=8|pages=1379–1388|pmid=24548565|pmc=3996918 |doi=10.1016/j.febslet.2014.02.004|year=2014|bibcode=2014FEBSL.588.1379L }}</ref> This has led to the idea that pannexins may not form intercellular junctions in the same way connexins and innexins do and therefore should not use the same hemi-channel/channel naming.<ref>{{Cite journal |title=Pannexin channels are not gap junction hemichannels |journal=Channels |vauthors=Sosinsky GE, Boassa D, Dermietzel R, Duffy HS, Laird DW, MacVicar B, Naus CC, Penuela S, Scemes E, Spray DC, Thompson RJ, Zhao H, Dahl G |date=2011-05-01 |issue=3 |volume=5 |pages=193–197 |doi=10.4161/chan.5.3.15765 |pmid=21532340 |pmc=3704572 |doi-access=free}}</ref> Others have presented evidence based on genetic sequencing and overall functioning in tissues, that pannexins should still be considered part of the gap junction family of proteins despite structural differences. These researchers also note that there are still more groups of connexin [[orthologs]] to be discovered.<ref>{{Cite journal |title=Are there gap junctions without connexins or pannexins? |journal=BMC Ecol. Evol. |url= |last=Slivko-Koltchik |first=Georgy A. |date=2019-02-26 |issue=Suppl 1 |at=46 |volume=19 |doi=10.1186/s12862-019-1369-4|pmid=30813901 |pmc=6391747 |doi-access=free |bibcode=2019BMCEE..19S..46S }}</ref>

Gap junction channels formed from two identical hemichannels are called homotypic, while those with differing hemichannels are heterotypic. In turn, hemichannels of uniform protein composition are called [[homomeric]], while those with differing proteins are [[heteromeric]]. Channel composition influences the function of gap junction channels, and different connexins will not necessarily form heterotypic with all others.<ref name="partners">{{cite journal | last1=Hervé |first1=JC |last2= Bourmeyster |first2 = N | last3= Sarrouilhe |first3= D | last4= Duffy |first4 =HS |title= Gap junctional complexes: from partners to functions. |journal=Prog Biophys Mol Biol |date= May 2007|volume=94|issue=1–2 |pages=29–65 |doi= 10.1016/j.pbiomolbio.2007.03.010|pmid=17507078}}</ref>

Before innexins and connexins were well characterized, the genes coding for the connexin gap junction channels were classified in one of three groups (A, B and C; for example, {{Gene|GJA1}}, {{Gene|GJC1}}), based on gene mapping and [[sequence similarity]].<ref>{{cite journal|last1=Hsieh|first1=CL|last2=Kumar|first2=NM|last3=Gilula|first3=NB|last4=Francke|first4=U|title=Distribution of genes for gap junction membrane channel proteins on human and mouse chromosomes.|journal=Somatic Cell and Molecular Genetics|date=Mar 1991|volume=17|issue=2|pages=191–200|pmid=1849321|doi=10.1007/bf01232976|s2cid=44622463}}</ref><ref>{{cite journal|last1=Kumar|first1=NM|last2=Gilula|first2=NB|title=Molecular biology and genetics of gap junction channels.|journal=Seminars in Cell Biology|date=Feb 1992|volume=3|issue=1|pages=3–16|pmid=1320430|doi=10.1016/s1043-4682(10)80003-0}}</ref><ref>{{cite journal|last1=Kren|first1=BT|last2=Kumar|first2=NM|last3=Wang|first3=SQ|last4=Gilula|first4=NB|last5=Steer|first5=CJ|title=Differential regulation of multiple gap junction transcripts and proteins during rat liver regeneration.|journal=The Journal of Cell Biology|date=Nov 1993|volume=123|issue=3|pages=707–18|pmid=8227133|doi=10.1083/jcb.123.3.707|pmc=2200133}}</ref> However, connexin genes do not code directly for the expression of gap junction channels; genes can produce only the proteins that make up gap junction channels. An alternative naming system based on the protein's molecular weight is the most widely used (for example, connexin43=GJA1, connexin30.3=GJB4).