Editing Gap junction (section)

====Connexins====
The purification<ref>{{Cite journal|doi=10.1083/jcb.54.3.646 |title=The isolation of mouse hepatocyte gap junctions : Preliminary Chemical Characterization and X-Ray Diffraction |year=1972 |last1=Goodenough |first1=D. A. |last2=Stoeckenius |first2=W. |journal=The Journal of Cell Biology |volume=54 |issue=3 |pages=646–56 |pmid=4339819 |pmc=2200277}}</ref><ref>{{Cite journal|doi=10.1083/jcb.61.2.557 |title=Bulk isolation of mouse hepatocyte gap junctions : Characterization of the Principal Protein, Connexin |year=1974 |last1=Goodenough |first1=D. A. |journal=The Journal of Cell Biology |volume=61 |pages=557–63 |pmid=4363961 |issue=2 |pmc=2109294}}</ref> of the intercellular gap junction plaques enriched in the channel forming protein ([[connexin]]) showed a protein forming hexagonal arrays in [[x-ray diffraction]]. Because of this, the systematic study and identification of the predominant [[gap junction protein]]<ref>{{Cite journal|doi=10.1083/jcb.103.3.767 |title=Cloning and characterization of human and rat liver cDNAs coding for a gap junction protein |year=1986 |last1=Kumar |first1=N. M. |journal=The Journal of Cell Biology |volume=103 |pages=767–76 |pmid=2875078 |first2=NB |issue=3 |pmc=2114303 |last2=Gilula}}</ref> became possible. 
Refined ultrastructural studies by TEM<ref>{{cite journal |vauthors=McNutt NS, Weinstein RS |title=The ultrastructure of the nexus. A correlated thin-section and freeze-cleave study |journal=J. Cell Biol. |volume=47 |issue=3 |pages=666–88 |date=December 1970 |pmid=5531667 |pmc=2108148 |doi=10.1083/jcb.47.3.666}}</ref><ref>{{Cite journal|doi=10.1083/jcb.47.1.49 |title=An interpretation of liver cell membrane and junction structure based on observation of freeze-fracture replicas of both sides of the fracture |year=1970 |last1=Chalcroft |first1=J. P. |journal=The Journal of Cell Biology |volume=47 |pages=49–60 |pmid=4935338 |first2=S |issue=1 |pmc=2108397 |last2=Bullivant}}</ref> showed protein occurred in a complementary fashion in both cells participating in a gap junction plaque. The gap junction plaque is a relatively large area of membrane observed in TEM [[thin section]] and freeze fracture (FF) seen filled with transmembrane proteins in both tissues and more gently treated gap junction preparations. With the apparent ability for one protein alone to enable intercellular communication seen in gap junctions<ref>{{Cite journal|pmid=3815522 |year=1987 |author1=Young |first2=ZA |first3=NB |title=Functional assembly of gap junction conductance in lipid bilayers: demonstration that the major 27 kd protein forms the junctional channel |volume=48 |issue=5 |pages=733–43 |journal=Cell |doi=10.1016/0092-8674(87)90071-7 |last2=Cohn |last3=Gilula|s2cid=39342230 }}</ref> the term gap junction tended to become synonymous with a group of assembled connexins though this was not shown in vivo. Biochemical analysis of gap junction isolated from various tissues demonstrated a family of connexins.<ref>{{Cite journal |year=1985 |vauthors=Nicholson BJ, Gros DB, Kent SB, Hood LE, Revel JP |title=The Mr 28,000 gap junction proteins from rat heart and liver are different but related |volume=260 |issue=11 |pages=6514–6517 |journal=The Journal of Biological Chemistry |doi=10.1016/S0021-9258(18)88810-X |doi-access=free |pmid=2987225 }}</ref><ref>{{Cite journal |doi=10.1083/jcb.105.6.2621 |title=Connexin43: a protein from rat heart homologous to a gap junction protein from liver |year=1987 |vauthors=Beyer EC, Paul DL, Goodenough DA |journal=The Journal of Cell Biology |volume=105 |pages=2621–2629 |pmid=2826492 |issue=6 Pt 1 |pmc=2114703}}</ref><ref>{{Cite journal |pmid=3891760 |year=1985 |vauthors=Kistler J, Kirkland B, Bullivant S |title=Identification of a 70,000-D protein in lens membrane junctional domains |volume=101 |issue=1 |pages=28–35 |pmc=2113615 |journal=The Journal of Cell Biology |doi=10.1083/jcb.101.1.28}}</ref>

The ultrastructure and biochemistry of isolated gap junctions already referenced had indicated the connexins preferentially group in gap junction plaques or domains and connexins were the best characterized constituent. It has been noted that the organisation of proteins into arrays with a gap junction plaque may be significant.<ref name="ReferenceA"/><ref>{{cite journal|author1-link=Lucas Andrew Staehelin |vauthors=Staehelin LA |title=Three types of gap junctions interconnecting intestinal epithelial cells visualized by freeze-etching |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=69 |issue=5 |pages=1318–21 |date=May 1972 |pmid=4504340 |pmc=426690 |bibcode=1972PNAS...69.1318S |doi=10.1073/pnas.69.5.1318 |doi-access=free}}</ref> It is likely this early work was already reflecting the presence of more than just connexins in gap junctions. Combining the emerging fields of freeze-fracture to see inside membranes and [[immunocytochemistry]] to label cell components (Freeze-fracture replica immunolabelling or FRIL and thin section immunolabelling) showed gap junction plaques in vivo contained the connexin protein.<ref>{{Cite journal|pmid=3818793 |year=1987 |last1=Gruijters |first1=WTM |first2=J |first3=S |first4=DA |title=Immunolocalization of MP70 in lens fiber 16-17-nm intercellular junctions |volume=104 |issue=3 |pages=565–72 |pmc=2114558 |journal=The Journal of Cell Biology |doi=10.1083/jcb.104.3.565 |last2=Kistler |last3=Bullivant |last4=Goodenough}}</ref><ref name="Gruijters"/> Later studies using [[immunofluorescence]] microscopy of larger areas of tissue clarified diversity in earlier results. Gap junction plaques were confirmed to have variable composition being home to connexon and non-connexin proteins as well making the modern usage of the terms "gap junction" and "gap junction plaque" non-interchangeable.<ref name="Gruijters, WTM 1989 509–13">{{Cite journal|pmid=2691517 |journal=Journal of Cell Science |title=A non-connexon protein (MIP) is involved in eye lens gap-junction formation |volume=93 |issue=3 |pages=509–513 |last1=Gruijters |first1=WTM |year=1989|doi=10.1242/jcs.93.3.509 |url=http://jcs.biologists.org/cgi/content/abstract/93/3/509|url-access=subscription }}</ref> To summarize, in early literature the term "gap junction" referred to the regular gap between membranes in vertebrates and non-vertebrates apparently bridged by "globules". The junction correlated with the cell's ability to directly couple with its neighbors through pores in their membranes. Then for a while gap junctions were only referring to a structure that contains connexins and nothing more was thought to be involved. Later, the gap junction "plaque" was also found to contain other molecules that helped define it and make it function.