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

The inhibition of gap-junctional intercellular communication (GJIC) between initiated and surrounding normal cells by tumor promoters is believed to be important in the promotion stage of carcinogenesis. Therefore, we examined the effect of skin-tumor promoters on the expression of the gap-junctional proteins connexin (Cx) 26, Cx43, and Cx31.1 in SENCAR mouse skin. Animals were treated with 12-0-tetradecanoylphorbol-13-acetate (TPA) (8.3 nmol), okadaic acid (OA) (2.5 nmol), chrysarobin (220 nmol), or benzoyl peroxide (BzPo) (83 micromol). Northern blot and immunofluorescence analyses revealed that keratinocytes in adult mouse skin expressed Cx31.1 and Cx43 but not Cx26. All four of the skin-tumor promoters switched on the Cx26 gene, transiently increased expression of Cx43, and significantly inhibited the expression of Cx31.1. The time courses for changes in Cx26, Cx3l. 1, and Cx43 mRNA levels coincided in most cases and in general corresponded well to the time-response curves for hyperplastic changes in mouse skin. The peaks of Cx26 and Cx43 expression and Cx31.1 inhibition appeared 12 h after TPA application and 24 h after OA and chrysarobin application. BzPo elevated the levels of Cx26 and Cx43 transcripts later (peak at 2-4 d). In tumor promoter-treated skin, Cx26 and Cx43 plaques were on the plasma membrane of most keratinocytes. Cx31.1 staining was much weaker than in untreated epidermis. Thus, tumor promoters induce a large change in the expression of several Cxs, which in turn may affect both the level of GJIC and the sensitivity of GJlC to regulatory factors.
Mol Carcinog 1996 Mar
PMID:Effect of diverse tumor promoters on the expression of gap-junctional proteins connexin (Cx)26, Cx31.1, and Cx43 in SENCAR mouse epidermis. 859 33

We have used low stringency hybridization to clone a novel connexin from a skate retinal cDNA library. A rat connexin 32 clone was used to isolate a single partial clone that was subsequently used to isolate seven more overlapping clones of the same cDNA. Two clones containing the entire open reading frame have a consensus sequence of 1456 bp and predict a protein of 302 amino acids length and molecular mass of 35,044 daltons, referred to as connexin 35 or Cx35. Southern blot analysis suggests that the cloned sequence lies in a single gene with one intron. Polymerase chain reaction amplification from genomic DNA and partial sequencing of this intron showed that it was approximately 950 bp in length, and located within the coding region 71 bp after the translation start site. Hydropathy analysis of the predicted protein and alignments with previously cloned connexins indicate that Cx35 has a long cytoplasmic loop and a relatively short carboxyl terminal tail. Multiple sequence alignments show that Cx35 has similarities to both alpha and beta groups of connexins and suggests that its origins may be near the divergence point for the two groups. Consensus sequences consistent with sites for phosphorylation by protein kinase C and by cAMP - or cGMP -dependent protein kinase were identified. Two transcripts were detected in Northern blot analysis: a 1.95-kb primary transcript and a 4.6-kb minor transcript. In RNA samples from 10 tissues, transcripts were detected only in the retina.
Mol Biol Cell 1996 Feb
PMID:Connexin 35: a gap-junctional protein expressed preferentially in the skate retina. 868 55

We have characterized the function of connexin (Cx) 32 gene mutations found in X-linked dominant Charcot-Marie-Tooth disease with respect to their ability to form functional gap junctions among themselves and to inactivate wild-type Cx32 by a dominant negative mechanism. We prepared four types of Cx32 mutant cDNAs and transfected them into HeLa cells, which do not show detectable levels of gap junctional intercellular communication (GJIC), nor expression of any connexins examined. Cells transfected with the wild-type Cx32 gene, but not those transfected with three different base substitution mutations (i.e. Cys 60 to Phe, Val 139 to Met, and Arg 215 to Trp), restored GJIC. Unexpectedly, in cells transfected with a nonsense mutant at codon 220, there was also restored GJIC. When we double-transfected these mutant constructs into the HeLa cells that had already been transfected with the wild-type Cx32 gene and thus were GJIC proficient, three base substitution mutants inhibited GJIC, suggesting that these three mutants can eliminate the function of wild-type Cx32 in a dominant negative manner. The nonsense mutation at codon 220 did not show such a dominant negative effect. Since both mutant and wild-type Cx32 mRNAs were detected, but only poor Cx32 protein expression at cell-cell contact areas was observed in the double transfectants, it is suggested that certain mutants form nonfunctional chimeric connexons with wild-type connexins, which are not properly inserted into the cytoplasmic membrane.
Mol Biol Cell 1996 Jun
PMID:Connexin 32 mutations from X-linked Charcot-Marie-Tooth disease patients: functional defects and dominant negative effects. 881 97

Connexins (Cx) are protein components of gap junction channels that permit the passage of small molecules between neighboring cells. cDNAs of a large family of connexins have been isolated and sequenced. A gap junction channel consists of two connexons, one from each cell in contact, composed of six connexin subunits. It has been suggested by Musil and coworkers that the oligomerization of formation of a connexon occurs at the level of the trans-Golgi network. In the present study, we initiated an analysis of the early stages of protein synthesis and membrane insertion of Cx32 and Cx26, two connexins that we have demonstrated are co-expressed in the same junctions in hepatocytes. Using an in vitro transcription and a coupled cell-free translation and translocation system, we observed that both Cx32 and Cx26 could insert into microsome membranes co-translationally, producing a topological structure indistinguishable from that in isolated gap junctions. To our surprise, Cx26 could also insert into membranes post-translationally with a native orientation. This post-translational membrane insertion process is dependent on nucleotides but not their hydrolysis. Cx32, on the other hand, could not insert into membranes post-translationally. These disparate properties of Cx32 and Cx26 are not due to the significant difference in the lengths of their C-terminal domains, but rather to their internal amino acid sequences. These observations raise the possibility that there may be another pathway for Cx26 to insert into membranes in cells and this feature may be important for the regulation of its functions. These findings may also lead us to a new approach to reconstitution without detergent extraction.
Mol Biol Cell 1996 Mar
PMID:Membrane integration of in vitro-translated gap junctional proteins: co- and post-translational mechanisms. 886 74

Murine connexin 40 (Cx40) and connexin 43 (Cx43) do not form functional heterotypic gap junction channels. This property may contribute to the preferential propagation of action potentials in murine conductive myocardium (expressing Cx40) which is surrounded by working myocardium, expressing Cx43. When mouse Cx40 and Cx43 were individually expressed in cocultured human HeLa cells, no punctate immunofluorescent signals were detected on apposed plasma membranes between different transfectants, using antibodies specific for each connexin, suggesting that Cx40 and Cx43 hemichannels do not dock to each other. We wanted to identify domains in these connexin proteins which are responsible for the incompatibility. Thus, we expressed in HeLa cells several chimeric gene constructs in which different extracellular and intracellular domains of Cx43 had been spliced into the corresponding regions of Cx40. We found that exchange of both extracellular loops (E1 and E2) in this system (Cx40*43E1,2) was required for formation of homotypic and heterotypic conductive channels, although the electrical properties differed from those of Cx40 or Cx43 channels. Thus, the extracellular domains of Cx43 can be directed to form functional homo- and heterotypic channels. Another chimeric construct in which both extracellular domains and the central cytoplasmic loop (E1, E2, and C2) of Cx43 were spliced into Cx40 (Cx40*43E1,2,C2) led to heterotypic coupling only with Cx43 and not with Cx40 transfectants. Thus, the central cytoplasmic loop of Cx43 contributed to selectivity. A third construct, in which only the C-terminal domain (C3) of Cx43 was spliced into Cx40, i.e., Cx40*43C3, showed neither homotypic nor heterotypic coupling with Cx40 and Cx43 transfectants, suggesting that the C-terminal region of Cx43 determined incompatibility.
Mol Biol Cell 1996 Dec
PMID:Incompatibility of connexin 40 and 43 Hemichannels in gap junctions between mammalian cells is determined by intracellular domains. 897 Jan 60

A total of 74 human embryos were stained with gap junction protein specific anti-peptide antibodies an antibodies to the desmosomal protein desmoplakin to reveal the expression pattern of intercellular junctions during preimplantation development. Prior to implantation, the human embryo expresses predominantly connexin (Cx43)-containing gap junctions. Gap junctions were first detected in apposing cell membranes at the 4-cell stage and became increasingly organized as development proceeded. In normal blastocysts, trophectoderm (TE) cells were linked by dense arrays of gap junctions while inner cell mass (ICM) cells were linked by small, punctate gap junctions. Gap junctions containing Cx32 or Cx26 were observed occasionally in the TE of late blastocysts. Desmosomes appeared between outer cells prior to cavitation and were retained in the TE, but not in the ICM. Levels of gap junction protein expression were variable in morphologically normal embryos at the same stage, suggesting that a normal appearance may not be a reliable indicator of future viability. Morphologically normal embryos often possessed multinucleate, apoptotic and decompacting cells. They could show either extensive, disorganized over-expression or reduced expression of gap junction protein. The results fit the view that only embryos destined to survive display an organized pattern of intercellular junctions.
Mol Hum Reprod 1996 Aug
PMID:Expression of intercellular junctions during preimplantation development of the human embryo. 923 75

We have previously shown that the protein connexin-43 which forms the connexons in gap junctions is present in the human corpus luteum. Abundant expression of connexin-43 is seen in the mid-luteal phase corpora lutea. Since the formation of gap junctions in a tissue requires the presence of adherens junctions formed by the cadherins, our aim in these studies was firstly to localize immunocytochemically E-cadherin and beta-catenin (a cytoplasmic protein associated with E-cadherin) in the human corpus luteum, and secondly to determine the concentrations of these proteins in the early, mid- and late luteal phase human corpora lutea. E-cadherin was localized to the periphery of luteal cells and was not detected in non-luteal tissue. beta-catenin was observed in the cytoplasm of the luteal cells. Abundant expression of E-cadherin was observed by Western analysis in the early luteal phase and the level of expression was significantly different from that observed in the mid- and late luteal phase corpora lutea. In contrast the concentrations of beta-catenin were higher in the mid-luteal phase compared to the early luteal phase. The differential expression of the cell adhesion molecule E-cadherin suggests that it may play a significant role in cell-to-cell communication in the corpus luteum, and in the cyclic development and demise of this tissue.
Mol Hum Reprod 1996 Oct
PMID:Immunocytochemical localization and expression of E-cadherin and beta-catenin in the human corpus luteum. 923 93

The expression of gap junction connexins (Cx) in the female reproductive tract of rodents and in the human endometrium is highly regulated by steroid hormones. Here we have investigated the distribution and regulation properties of Cx43, Cx26 and Cx32 in the human ectopic endometrium of 41 patients, using immunohistochemistry. The biopsies were obtained during the early or late follicular phase (26 cases), during the corpus luteum phase (five cases) and after a 6 month treatment with a gonadotrophin-releasing hormone (GnRH) agonist (three cases) or progestin (seven cases). Aberrant expression of Cx43 was found in the epithelium of nearly all endometriotic glands whereas Cx26, typical for human uterine epithelium cells, was only detected in 18 cases; in 17 it was co-expressed with Cx43. The stromal compartment of the tissues did not express any connexins investigated. Staining for Cx32 was absent in all endometriotic tissues. Strong expression of Cx43 was correlated with a high serum value of 17 beta-oestradiol, whereas a strong expression of Cx26 was found with high values of progesterone mainly in patients after progestin treatment. The epithelium of endometriotic implants collected after GnRH agonist treatment expressed Cx26 and Cx43 only moderately. The patterns described demonstrate an aberrant connexin expression and a different hormonal regulation pattern in endometriotic tissues compared to the normal cyclic uterine endometrium, thus indicating a high dedifferentiation from the normal situation. However, endometriosis still remains a hormonally-dependent benign disease, and hence, can be treated hormonally.
Mol Hum Reprod 1997 May
PMID:Aberrant expression pattern of gap junction connexins in endometriotic tissues. 923 21

The expression of mRNA for connexin 43, a gap junction protein putatively found in astrocytes, is studied in two experimental models of epilepsy: the electrically kindled rat and the tetanus-toxin-injected rat. Rats were kindled by electrical stimulation of the amygdala to Racine class 5 seizures and divided into cohorts of three to undergo 3, 6, or 10 such events, respectively. Another two cohorts of rats received injections of tetanus toxin at strengths of 3 and 9 MLD50, respectively, into the amygdala. Features of epileptogenicity were identified electrographically in both cohorts during the first 4 wk following toxin injection with spontaneous ictal events recorded in the latter cohort. All rats were sacrificed 4 wk after electrode or cannula implantation, except for two toxin-injected cohorts that were sacrificed at wk 8 or 10. The epileptogeonic area in the region of the amygdala was harvested and pooled by cohort for Northern blot analysis. These were compared with control nonimplanted tissues. In the tetanus-toxin-injected animals, at time-points of 4, 8, and 10 wk, connexin 43 mRNA expression in epileptogenic tissues is found to be decreased or unchanged relative to control cases. Kindled rats demonstrated reductions of connexin mRNA with a trend toward normalizing levels with increasing numbers of stimulations when compared to control animals. Connexin 43 immunostained sections of the basolateral amygdala showed a similar trend in protein expression. Both experimental models of epilepsy show no connexin 43 mRNA upregulation despite varying degrees of epileptogenicity. This study therefore does not support the hypothesis that an increase in transcription is the basis for any proposed increase in gap junction communication involving connexin 43 in the context of epileptogenicity or as a reaction to increased neuronal excitability.
Mol Chem Neuropathol
PMID:Connexin 43 mRNA expression in two experimental models of epilepsy. 943 59

Coordinated microscopic and molecular biological studies were used to document gap junction expression during postnatal development in ferret tracheal epithelium and lung and in fetal and adult human airway and lung. Expression of connexin 26 (Cx26) in the ferret airways was limited to the epithelial layer and was observed only during the newborn interval. In contrast, we found Cx26 expressed in the alveolar epithelium of the ferret lung by in situ hybridization, Northern blotting, RT-PCR amplification, and immunocytochemical labeling at all ages examined. This finding was further confirmed by documentation of gap junctional plaques upon ultrastructural examination of freeze-fracture replicas of adult ferret lung tissue. Parallel studies of developing human fetal lung and airway suggested connexin expression in the airways only in the first trimester but, as in the ferret, persistent expression was observed in both fetal and adult lung. These studies suggest that the transient expression of Cx26 is a reliable early indicator of airway epithelial development and differentiation in the airways. In contrast, Cx26 expression persists throughout life in the lung, suggesting that gap junctions serve more perennial intercellular communication functions in the peripheral lung.
Am J Respir Cell Mol Biol 1998 Jan
PMID:Connexin 26 expression in human and ferret airways and lung during development. 944 52


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