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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the mechanism by which cyclic AMP (cAMP) induces gap junctional communication via cell-to-cell channels in a communication-deficient rat Morris hepatoma cell line. We found that under basal conditions, the cells transcribe cx43 at a low level but do not transcribe cx26 or cx32. Elevation of intracellular cAMP, which induced communication, increased cx43 mRNA 15- to 40-fold and the rate of cx43 transcription 6-fold. Cx43 protein was detected by immunostaining in junctions of only those cells in which communication had been induced. We found the regulation by cAMP also in other cell lines; namely, in those with a low basal level of cx43 mRNA.
Mol Biol Cell 1992 Aug
PMID:Transcription of the gene for the gap junctional protein connexin43 and expression of functional cell-to-cell channels are regulated by cAMP. 132 97

The connexin genes Cx31 and Cx45 coding for proteins of gap junctional subunits have been assigned to mouse chromosomes 4 and 11 by Southern blot hybridization of specific gene probes to DNA from mouse x Chinese hamster somatic cell hybrids. In addition, our results confirm the recent assignment of mouse connexin genes Cx26, Cx32, Cx37, Cx40, Cx43, and Cx46 to mouse chromosomes 14, X, 4, 3, 10, and 14, respectively, by analysis of interspecific backcrosses and by somatic cell hybridization. Our assignment of the Cx31 gene to mouse chromosome 4 locates the fourth connexin gene on this mouse chromosome to which the genes for Cx31.1, Cx37, and Cx30.3 have previously been assigned. Interestingly three of them (coding for Cx31, Cx31.1, and Cx30.3) are preferentially expressed in skin. Possibly some of the connexin genes clustered on mouse chromosome 4 may be regulated coordinately.
Somat Cell Mol Genet 1992 Jul
PMID:Chromosomal assignments of mouse connexin genes, coding for gap junctional proteins, by somatic cell hybridization. 133 96

The membrane topology and quaternary structure of rat cardiac gap junction ion channels containing alpha 1 connexin (i.e. Cx43) have been examined using anti-peptide antibodies directed to seven different sites in the protein sequence, cleavage by an endogenous protease in heart tissue and electron microscopic image analysis of native and protease-cleaved two-dimensional membrane crystals of isolated cardiac gap junctions. Specificity of the peptide antibodies was established using dot immunoblotting, Western immunoblotting, immunofluorescence and immunoelectron microscopy. Based on the folding predicted by hydropathy analysis, five antibodies were directed to sites in cytoplasmic domains and two antibodies were directed to the two extracellular loop domains. Isolated gap junctions could not be labeled by the two extracellular loop antibodies using thin-section immunogold electron microscopy. This is consistent with the known narrowness of the extracellular gap region that presumably precludes penetration of antibody probes. However, cryo-sectioning rendered the extracellular domains accessible for immunolabeling. A cytoplasmic "loop" domain of at least Mr = 5100 (residues (101 to 142) is readily accessible to peptide antibody labeling. The native Mr = 43,000 protein can be protease-cleaved on the cytoplasmic side of the membrane, resulting in an Mr approximately 30,000 membrane-bound fragment. Western immunoblots showed that protease cleavage occurs at the carboxy tail of the protein, and the cleavage site resides between amino acid residues 252-271. Immunoelectron microscopy demonstrated that the Mr approximately 13,000 carboxy-terminal peptide(s) is released after protease cleavage and does not remain attached to the Mr approximately 30,000 membrane-bound fragment via non-covalent interactions. Electron microscopic image analysis of two-dimensional membrane crystals of cardiac gap junctions revealed that the ion channels are formed by a hexagonal arrangement of protein subunits. This quaternary arrangement is not detectably altered by protease cleavage of the alpha 1 polypeptide. Therefore, the Mr approximately 13,000 carboxyterminal domain is not involved in forming the transmembrane ion channel. The similar hexameric architecture of cardiac and liver gap junction connexins indicates conservation in the molecular design of the gap junction channels formed by alpha or beta connexins.
J Mol Biol 1992 Feb 20
PMID:Membrane topology and quaternary structure of cardiac gap junction ion channels. 137 48

Variants of the Cx43 gap junction protein have been detected on Western immunoblots by using an antipeptide antibody to the N-terminus of the protein. In heart ventricle, atrium, brain, retina, and uterus, different yet characteristic ratios of a broad 43-kDa band and a 39- to 40-kDa doublet were observed. These proteins (in lens epithelium, testes, and spleen) or their messages (in stomach, duodenum, kidney, and lung) were also detected in several nonexcitable systems but at consistently lower levels than found in electrically excitable tissues. The reproducible heterogeneity in electrophoretic mobility of Cx43 seen in different tissues does not appear to be due to proteolysis, since both the 43-kDa band and the 39- to 40-kDa doublet were recognized by an N-terminal as well as a C-terminal antibody. Furthermore, Northern (RNA) blots from different tissues show that both polypeptide profiles arise from indistinguishable transcripts. The conversion by alkaline phosphatase treatment of a predominantly 43-kDa profile (in heart) to a 39- to 40-kDa profile (characteristic of brain and protein translated in vitro from the RNA) suggests that the observed electrophoretic heterogeneity arises from tissue-wide differences in the phosphorylation state of Cx43.
Mol Cell Biol 1991 Jan
PMID:Tissue-specific distribution of differentially phosphorylated forms of Cx43. 184 23

Gap junctions are widely distributed structures that mediate communication between cells. The channels that allow passage of small molecules between adjacent cells are made up of oligomeric proteins (connexins) that are encoded by a family of related genes. By probing somatic cell hybrid DNA on Southern filters with rat or human cDNAs or human genomic fragments, we have mapped four functioning gap junction genes, (alpha 1, beta 1, beta 2, and alpha 3), to different sites on human chromosomes: GJA1 (connexin43) to 6p21.1-q24.1; GJB1 (connexin32) to Xcen-q22; GJB2 (connexin26) to 13; and GJA3 (connexin46) also to 13, probably near GJB2. The GJA3 probe also hybridized to a restriction fragment that was mapped to chromosome 1. A GJA1-related pseudogene GJA1P was assigned to chromosome 5. The homologous loci in mouse were assigned to regions of known conserved syntenic groups: Gja-1 to chromosome 10; Gjb-1 to XD-F4 and Gjb-2 to 14. Of two sites of hybridization with the GJA3 probe, on mouse 14 and 5, we assume that the site on 14 corresponds to the GJA3 locus on human 13. Based on these data, additional members of this family of related genes can be isolated and characterized, and possible human and mouse mutations can be identified.
Somat Cell Mol Genet 1991 Mar
PMID:Distribution of genes for gap junction membrane channel proteins on human and mouse chromosomes. 184 21

One consequence of the diversity in gap junction structural proteins is that cells expressing different connexins may come into contact and form intercellular channels that are mixed in connexin content. We have systematically examined the ability of adjacent cells expressing different connexins to communicate, and found that all connexins exhibit specificity in their interactions. Two extreme examples of selectivity were observed. Connexin40 (Cx40) was highly restricted in its ability to make heterotypic channels, functionally interacting with Cx37, but failing to do so when paired with Cx26, Cx32, Cx43, Cx46, and Cx50. In contrast, Cx46 interacted well with all connexins tested except Cx40. To explore the molecular basis of connexin compatibility and voltage gating, we utilized a chimera consisting of Cx32 from the N-terminus to the second transmembrane domain, fused to Cx43 from the middle cytoplasmic loop to the C-terminus. The chimeric connexin behaved like Cx43 with regard to selectivity and like Cx32 with regard to voltage dependence. Taken together, these results demonstrate that the second but not the first extracellular domain affects compatibility, whereas voltage gating is strongly influenced by sequences between the N-terminus and the second transmembrane domain.
Mol Biol Cell 1995 Apr
PMID:Functional analysis of selective interactions among rodent connexins. 754 41

A reduction of gap-junctional intercellular communication (GJIC) often accompanies neoplastic transformation. The present work demonstrates that transformation by the oncogenic human DNA virus, human papilloma virus 16(HPV16), also reduces GJIC between L6 rat myoblasts. HPVs are associated with anogenital cancers, the incidence of which is increasing in HIV positive patients of both sexes. Using videofluorescence imaging of Fura-2 loaded cells a lack of GJIC between transformed HPV16-L6 cells was first indicated by uncoordinated brief [Ca2+]i spikes in clusters of DMSO-treated HPV16-L6 cells instead of the synchronous, sustained [Ca2+]i surges in clusters of DMSO-treated L6 cells. Reduced GJIC between HPV16-L6 cells was demonstrated directly by a much reduced transfer of lucifer yellow dye from HPV16-L6 cells, which had been loaded with the dye through electroporation with an EPIZAP II in situ electroporator, to neighbouring nonelectroporated HPV16-L6 cells. One reason for this reduced GJIC between HPV16-L6 cells could have been their dramatically enhanced activity of membrane-associated PKC which is known to phosphorylate connexins and down-regulate gap junctions. However, the main reason was the viral-induced inhibition of the expression of a major gap junction component, Cx43 (Connexin 43), in the transformed myoblasts.
Cell Mol Biol (Noisy-le-grand) 1995 Jun
PMID:Alterations in cell-cell communication in human papillomavirus type 16 (HPV16) transformed rat myoblasts. 754 85

We characterized the expression of two gap junction genes (Cx26 and Cx43) in the mouse decidua and placenta. In the decidua, in situ hybridization analysis and immunostaining studies revealed a high level of Cx43 expression. In contrast, Cx26 expression was not detected. Analysis of the placenta revealed that both Cx43 and Cx26 transcripts are expressed, but in nonoverlapping cell populations. Cx26 transcripts were observed only in the labyrinthine trophoblast layer of the placenta, a tissue of ectoplacental cone derivation. In contrast, no Cx43 transcripts were found in the placenta proper, but only in the maternally derived decidual cap covering the placenta. These results, in conjunction with previous observations in the mouse and rat, indicate that there may be species-specific differences in the pattern of Cx43/Cx26 expression in the placenta and decidua.
Mol Reprod Dev 1995 Jun
PMID:Nonoverlapping expression of Cx43 and Cx26 in the mouse placenta and decidua: a pattern of gap junction gene expression differing from that in the rat. 765 73

Gap junctions (GJ) are membrane specializations responsible for intercellular communication and for ensuring electrical and/or metabolic coupling between cells. They are composed of connexins, a family of related proteins. Connexin-43 (Cx43) is a major connexin of the rat heart, expressed by myocytes as well as non-muscle cells. In this communication we have examined expression of Cx43 by cardiac fibroblasts and regulation of its expression by an endogenous mitogen, basic fibroblast growth factor (bFGF). Recombinant human bFGF, administered to cultured cells which had been maintained in 0.5% serum for 48 h, induced dose-dependent and statistically significant increases in Cx43 mRNA as well as protein accumulation, at 6 h after addition. Intercellular communication was also increased at 6 h but not 30 min after bFGF treatment, as assessed using a scrape-loading protocol. It is concluded that the bFGF-induced stimulation of Cx43 expression caused increased coupling between cardiac fibroblasts. This would be of importance in injured myocardium, the increased bFGF content of which might stimulate electrical coupling involving fibroblasts of the scar tissue.
Mol Cell Biochem 1995 Feb 09
PMID:Basic fibroblast growth factor stimulates connexin-43 expression and intercellular communication of cardiac fibroblasts. 777 63

Gap-junctional intercellular communication (GJIC) in normal rat liver cells involves at least three different connexins (Cxs)--Cx32, Cx26, Cx43--depending on the cell type, position in the lobule, or both. Whereas rat hepatocyte primary cultures expressed Cx32 and Cx26 as observed in vivo, cell lines derived from normal rat liver (WB-F344, Clone 9, RLEC, and BRL) expressed Cx43 and to a lesser extent Cx26. Hepatoma cells propagated in vitro were either deficient in GJIC and Cx expression (7777, 8994, H4IIE-C3) or communicated via gap junctions composed of Cx43 protein (N1S1-67, 9618A). Analysis of neoplasms that resulted from injection of hepatoma cells into rat femoral muscle showed differences in Cx expression when compared with cells grown in vitro. Whereas hepatoma cells 7777 and H4IIE-C3 failed to express Cx mRNAs in culture, these cells transplanted in vivo expressed levels of Cx32 mRNA comparable to those in normal liver. However, detectable Cx32 immunostaining was observed in less than 5% of the neoplastic cells in vivo. These results indicate that Cx32 protein was posttranscriptionally downregulated in 7777 and H4IIE-C3 tumor cells. Unexpectedly, 9618A cells expressed Cx43 mRNA and protein in cell culture but expressed Cx32 mRNA in vivo. In contrast, N1S1 transplants continued to express Cx43 mRNA and protein in vivo. Unlike the punctate Cx43 staining observed in suspension cultures of N1S1 cells, diffuse intracellular Cx43 staining was observed in N1S1-derived neoplasms in vivo, although the electrophoretic pattern of Cx43 isolated from N1S1 tumors grown in vivo (43 kDa) was different from that observed in suspension cell cultures (43 and 45 kDa). Thus, the findings reported here demonstrate that Cx expression in hepatoma cells depends on the environment, whether in vivo or in vitro, in which the cells are propagated.
Mol Carcinog 1994 Nov
PMID:Differences in the expression of connexin genes in rat hepatomas in vivo and in vitro. 794 3


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