Editing Gap junction (section)

====The "plaque" or "formation plaque"====
[[File:Connexin43-Modulates-Cell-Polarity-and-Directional-Cell-Migration-by-Regulating-Microtubule-Dynamics-pone.0026379.s004.ogv|right|thumb|[[Immunofluorescence]] microscopy video of connexins being moved along [[microtubule]]s to the surface of a cell at 2.7 times normal speed.<ref name="ReferenceB"/>]]
Early descriptions of ''gap junctions'', ''connexons'' or ''innexons'' did not refer to them as such; many other terms were used. It is likely that ''synaptic disks''<ref>{{cite journal | pmid = 14069795 | pmc=2106854 | volume=19 | title=The occurrence of a subunit pattern in the unit membranes of club endings in mauthner cell synapses in goldfish brains |date=October 1963 | journal=J. Cell Biol. | pages=201–21 | doi = 10.1083/jcb.19.1.201 | last1 = Robertson | first1 = JD | issue = 1}}</ref> were an accurate reference to gap junction plaques. While the detailed structure and function of the connexon was described in a limited way at the time the gross ''disk'' structure was relatively large and easily seen by various TEM techniques. Disks allowed researchers using TEM to easily locate the connexons contained within the disk like patches in vivo and in vitro. The disk or ''plaque'' appeared to have structural properties different from those imparted by the connexons/innexons alone.<ref name=Hand72>{{cite journal | pmid = 4109925 | pmc=2108629 | volume=52 | issue=2 | title=The structural organization of the septate and gap junctions of Hydra |date=February 1972 | journal=J. Cell Biol. | pages=397–408 | doi = 10.1083/jcb.52.2.397 | last1 = Hand | first1 = AR | last2 = Gobel | first2 = S}}</ref> It was thought that if the area of membrane in the plaque transmitted signals, the area of membrane would have to be sealed in some way to prevent leakage.<ref>{{cite journal |vauthors=Loewenstein WR, Kanno Y |title=Studies on an epithelial (gland) cell junction. I. Modifications of surface membrane permeability |journal=J. Cell Biol. |volume=22 |pages=565–86 |date=September 1964 |pmid=14206423 |pmc=2106478 |doi=10.1083/jcb.22.3.565 |issue=3}}</ref>
Later studies showed gap junction plaques are home to non-connexin proteins, making the modern usage of the terms "gap junction" and "gap junction plaque" non-interchangeable as the area of the gap junction plaque may contain proteins other than connexins.<ref name="Gruijters, WTM 1989 509–13"/><ref name="Gruijters-vesicles"/> Just as connexins do not always occupy the entire area of the plaque, the other components described in the literature may be only long-term or short-term residents.<ref name=pmc3156236>{{cite journal |vauthors=Ozato-Sakurai N, Fujita A, Fujimoto T|title=The distribution of phosphatidylinositol 4,5-bisphosphate in acinar cells of rat pancreas revealed with the freeze-fracture replica labeling method |journal=PLOS ONE |volume=6 |issue=8 |pages=e23567 |year=2011 |pmid=21858170 |pmc=3156236 |doi=10.1371/journal.pone.0023567 |editor1-last=Wong |editor1-first=Nai Sum|bibcode = 2011PLoSO...623567O |doi-access=free }}</ref><ref name="partners" /><ref>{{cite journal |last1=Strauss |first1=RE |last2=Gourdie |first2=RG |title=Cx43 and the Actin Cytoskeleton: Novel Roles and Implications for Cell-Cell Junction-Based Barrier Function Regulation |journal=Biomolecules |date=December 2020 |volume=10 |issue=12 |page=1656 |doi=10.3390/biom10121656 |pmid=33321985|pmc=7764618 |doi-access=free }}</ref>

Studies allowing views inside the plane of the membrane of gap junctions during formation indicated that a "formation plaque" formed between two cells prior to the connexins moving in. They were particle free areas—when observed by TEM FF, indicated very small or no [[transmembrane protein]]s were likely present. Little is known about what structures make up the formation plaque or how the formation plaque's structure changes when connexins and other components move in and out. One of the earlier studies of the formation of small gap junctions describes rows of particles and particle free halos.<ref>{{cite journal | pmid = 4135001 | pmc=2109180 | volume=62 | issue=1 | title=Assembly of gap junctions during amphibian neurulation |date=July 1974 | journal=J. Cell Biol. | pages=32–47 | doi = 10.1083/jcb.62.1.32 | last1 = Decker | first1 = RS | last2 = Friend | first2 = DS}}</ref> With larger gap junctions they were described as formation plaques with connexins moving into them. The particulate gap junctions were thought to form 4–6 hours after the formation plaques appeared.<ref>{{cite journal | pmid = 1083855 | pmc=2109697 | volume=69 | issue=3 | title=Hormonal regulation of gap junction differentiation |date=June 1976 | journal=J. Cell Biol. | pages=669–85 | doi = 10.1083/jcb.69.3.669 | last1 = Decker | first1 = RS}}</ref> How the connexins may be transported to the plaques using [[tubulin]] is becoming clearer.<ref name="ReferenceB"/><ref>{{cite journal |vauthors=Lauf U, Giepmans BN, Lopez P, Braconnot S, Chen SC, Falk MM|title=Dynamic trafficking and delivery of connexons to the plasma membrane and accretion to gap junctions in living cells |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue=16 |pages=10446–51 |date=August 2002 |pmid=12149451 |pmc=124935 |doi=10.1073/pnas.162055899 |bibcode = 2002PNAS...9910446L |doi-access=free }}</ref>

The formation of plaque and the non-connexin part of the classical gap junction plaque have been difficult for early researchers to analyse. It appears in TEM FF and thin section to be a lipid membrane domain that can somehow form a comparatively rigid barrier to other lipids and proteins. There has been indirect evidence for certain lipids being preferentially involved with the formation plaque, however this cannot be considered definitive.<ref>{{cite journal | pmid = 1698798 | volume=96 | title=Increased gap junction assembly between cultured cells upon cholesterol supplementation |date=June 1990 | journal=J. Cell Sci. | pages=231–8 | issue=2 | last1 = Meyer | first1 = R | last2 = Malewicz | first2 = B | last3 = Baumann | first3 = WJ | last4 = Johnson | first4 = RG| doi=10.1242/jcs.96.2.231 }}</ref><ref>{{cite journal | pmid = 22049024 | doi=10.1091/mbc.E11-02-0141 | volume=23 | issue=1 | title=Gap junction assembly: roles for the formation plaque and regulation by the C-terminus of connexin43 | pmc=3248906 |date=January 2012 | journal=Mol. Biol. Cell | pages=71–86 | last1 = Johnson | first1 = R. G. | last2 = Reynhout | first2 = J. K. | last3 = Tenbroek | first3 = E. M. | last4 = Quade | first4 = B. J. | last5 = Yasumura | first5 = T. | last6 = Davidson | first6 = K. G. V. | last7 = Sheridan | first7 = J. D. | last8 = Rash | first8 = J. E.}}</ref> It is difficult to envisage breaking up the membrane to analyse membrane plaques without affecting their composition. By study of connexins still in membranes lipids associated with the connexins have been studied.<ref>{{cite journal | pmid = 19686581 | doi=10.1186/1741-7007-7-52 | volume=7 | title=Connexin channels and phospholipids: association and modulation | pmc=2733891 | year=2009 | journal=BMC Biol. | pages=52 | last1 = Locke | first1 = Darren | last2 = Harris | first2 = Andrew L | issue=1 | doi-access=free }}</ref> It was found that specific connexins tended to associate preferentially with specific phospholipids. As formation plaques precede connexins these results still give no certainty as to what is unique about the composition of plaques themselves. Other findings show connexins associate with protein scaffolds used in another junction, the zonula occludens [[Tight junction protein 1|ZO-1]].<ref name="Naomi Kamasawa PMC">{{cite journal |vauthors=Li X, Kamasawa N, Ciolofan C, etal |title=Connexin45-containing neuronal gap junctions in rodent retina also contain connexin36 in both apposing hemiplaques, forming bihomotypic gap junctions, with scaffolding contributed by zonula occludens-1 |journal=J. Neurosci. |volume=28 |issue=39 |pages=9769–89 |date=September 2008 |pmid=18815262 |pmc=2638127 |doi=10.1523/JNEUROSCI.2137-08.2008}}</ref> While this helps us understand how connexins may be moved into a gap junction formation plaque, the composition of the plaque itself is still somewhat sketchy. Some headway on the in vivo composition of the gap junction plaque is being made using TEM FRIL.<ref name=pmc3156236/><ref name="Naomi Kamasawa PMC"/>