scholarly journals Enhanced connexin 43 expression delays intra-mitoitc duration and cell cycle traverse independently of gap junction channel function

2010 ◽  
Vol 110 (3) ◽  
pp. 772-782 ◽  
Author(s):  
Scott R. Johnstone ◽  
Angela K. Best ◽  
Catherine S. Wright ◽  
Brant E. Isakson ◽  
Rachel J. Errington ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gap Junction ◽  
Connexin 43 ◽  
Channel Function ◽  
Gap Junction Channel

scholarly journals Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways

2015 ◽  
Vol 36 (3) ◽  
pp. 1210-1222 ◽  
Author(s):  
Aiqing Zhang ◽  
Ying Han ◽  
Bin Wang ◽  
Shanwen Li ◽  
Weihua Gan
Keyword(s):  
Gap Junction ◽  
Connexin 43 ◽  
Mesangial Cell ◽  
Lucifer Yellow ◽  
Inverse Correlation ◽  
Dye Transfer ◽  
Cx43 Expression ◽  
Pi3k Inhibitor Ly294002 ◽  
Channel Function ◽  
Gap Junction Channel

Aims: This study aimed to explore the precise mechanism and signaling pathways of mesangial cell (MC) proliferation from a new point of view considering Connexin 43 (Cx43). Methods: MC proliferation was measured by the incorporation of 3H-thymidine (3H-TdR). Cx43 was over-expressed in MC cells using lipofectamine 2000, and the expression level was tested with reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. The gap junction channel function was explored by Lucifer Yellow scrape loading and dye transfer (SLDT), and the intracellular calcium concentrations ([Ca2+]i) were characterized by confocal microscopy on cells loaded with Fura-3/AM. Results: There was an inverse correlation between Cx43 expression and MC proliferation (P<0.05). SLDT studies revealed that there was no difference in the gap junction channel function between the normal and Aldosterone (Aldo)-stimulated groups (P>0.05). Our data also showed that the mineralcorticoid receptor (MR) antagonist spironolactone, ERK1/2 inhibitor PD98059 and PKC inhibitor GF109203X could attenuate the down-regulation of Cx43 expression in Aldo-induced MC proliferation; however, the PI3K inhibitor LY294002 could block MC proliferation without affecting Cx43 expression at either the mRNA or protein level. In addition, Aldo promoted MC proliferation in parallel with increasing [Ca2+]i (P<0.05), suggesting that the classical PKC pathway might be activated. Conclusions: Our study provides preliminary evidence that Cx43 is an important regulator of Aldo-promoted MC proliferation. Furthermore, reduced Cx43 expression promoted MC proliferation independent of the gap junction channel function, and this process might be mediated through the ERK1/2- and PKC-dependent pathways.

scholarly journals Cholesterol modulates function of connexin 43 gap junction channel via PKC pathway in H9c2 cells

2014 ◽  
Vol 1838 (8) ◽  
pp. 2019-2025 ◽  
Author(s):  
Jun Zou ◽  
Xiao-Yang Yue ◽  
Sheng-Chao Zheng ◽  
Guangwei Zhang ◽  
He Chang ◽  
...  
Keyword(s):  
Gap Junction ◽  
Connexin 43 ◽  
H9c2 Cells ◽  
Gap Junction Channel

Distinctive gap junction channel types connect WB cells, a clonal cell line derived from rat liver

1991 ◽  
Vol 260 (3) ◽  
pp. C513-C527 ◽  
Author(s):  
D. C. Spray ◽  
M. Chanson ◽  
A. P. Moreno ◽  
R. Dermietzel ◽  
P. Meda
Keyword(s):  
Gap Junction ◽  
Cell Line ◽  
Rat Liver ◽  
Connexin 43 ◽  
Single Channel ◽  
Freeze Fracture ◽  
Particle Sizes ◽  
Frequency Distributions ◽  
Gap Junction Channel ◽  
Junctional Conductance

Gap junctions, dye coupling, and junctional conductance were studied in a cell line (WB) that is derived from rat liver and displays a phenotype similar to “oval” cells. In freeze-fracture replicas, two distinctive particle sizes were detected in gap junctional plaques. Immunocytochemical studies indicated punctate staining at membrane appositions using antibodies to connexin 43 and to a brain gap junction-associated antigen (34 kDa). No staining was observed using antibodies prepared against rat liver gap junction proteins (connexins 32 and 26). Pairs of WB cells were electrically and dye coupled. Junctional conductance (gj) between cell pairs averaged approximately 10 nS; occasionally, gj was low enough that unitary junctional conductances (gamma j) could be detected. Using a CsCl-containing electrode solution, distinctive gamma j values were recorded: approximately 20-30 pS, approximately 80-90 pS, and the sum of the other sizes. The largest gamma j events were apparently due to random coincident openings or closures of the smaller channels. Several treatments reduced gj. Frequency distributions of gamma j were unaltered by 2 mM halothane or 3.5 heptanol, but the sizes of intermediate and largest events were reduced slightly by 100 nM phorbol ester, and the relative frequency of the largest events was increased by 10 microM glutaraldehyde. We conclude that the distinctive gamma j values represent openings and closures of two distinct types of gap junction channels rather than substates of a single channel type; these unitary conductances may correspond to the dual immunoreactivity and to the two particle sizes seen in freeze fracture.

scholarly journals An Alternatively Translated Connexin 43 Isoform, GJA1-11k, Localizes to the Nucleus and Can Inhibit Cell Cycle Progression

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 473
Author(s):  
Irina Epifantseva ◽  
Shaohua Xiao ◽  
Rachel E. Baum ◽  
André G. Kléber ◽  
TingTing Hong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Gap Junction ◽  
Connexin 43 ◽  
Cell Cycle Progression ◽  
Tumor Formation ◽  
Full Length ◽  
Cycle Progression ◽  
Junction Protein ◽  
Truncated Isoforms

Connexin 43 (Cx43) is a gap junction protein that assembles at the cell border to form intercellular gap junction (GJ) channels which allow for cell–cell communication by facilitating the rapid transmission of ions and other small molecules between adjacent cells. Non-canonical roles of Cx43, and specifically its C-terminal domain, have been identified in the regulation of Cx43 trafficking, mitochondrial preconditioning, cell proliferation, and tumor formation, yet the mechanisms are still being explored. It was recently identified that up to six truncated isoforms of Cx43 are endogenously produced via alternative translation from internal start codons in addition to full length Cx43, all from the same mRNA produced by the gene GJA1. GJA1-11k, the 11kDa alternatively translated isoform of Cx43, does not have a known role in the formation of gap junction channels, and little is known about its function. Here, we report that over expressed GJA1-11k, unlike the other five truncated isoforms, preferentially localizes to the nucleus in HEK293FT cells and suppresses cell growth by limiting cell cycle progression from the G0/G1 phase to the S phase. Furthermore, these functions are independent of the channel-forming full-length Cx43 isoform. Understanding the apparently unique role of GJA1-11k and its generation in cell cycle regulation may uncover a new target for affecting cell growth in multiple disease models.

scholarly journals Gating of connexin 43 gap junctions by a cytoplasmic loop calmodulin binding domain

2012 ◽  
Vol 302 (10) ◽  
pp. C1548-C1556 ◽  
Author(s):  
Qin Xu ◽  
Richard F. Kopp ◽  
Yanyi Chen ◽  
Jenny J. Yang ◽  
Michael W. Roe ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Connexin 43 ◽  
Binding Domain ◽  
Cytoplasmic Loop ◽  
Inhibitory Peptide ◽  
Open Probability ◽  
Calmodulin Binding ◽  
Gap Junction Channel ◽  
Whole Cell Patch Clamp

Calmodulin (CaM) binding sites were recently identified on the cytoplasmic loop (CL) of at least three α-subfamily connexins (Cx43, Cx44, Cx50), while Cx40 does not have this putative CaM binding domain. The purpose of this study was to examine the functional relevance of the putative Cx43 CaM binding site on the Ca2+-dependent regulation of gap junction proteins formed by Cx43 and Cx40. Dual whole cell patch-clamp experiments were performed on stable murine Neuro-2a cells expressing Cx43 or Cx40. Addition of ionomycin to increase external Ca2+ influx reduced Cx43 gap junction conductance (Gj) by 95%, while increasing cytosolic Ca2+ concentration threefold. By contrast, Cx40 Gj declined by <20%. The Ca2+-induced decline in Cx43 Gj was prevented by pretreatment with calmidazolium or reversed by the addition of 10 mM EGTA to Ca2+-free extracellular solution, if Ca2+ chelation was commenced before complete uncoupling, after which gj was only 60% recoverable. The Cx43 CL136–158 mimetic peptide, but not the scrambled control peptide, or Ca2+/CaM-dependent kinase II 290–309 inhibitory peptide also prevented the Ca2+/CaM-dependent decline of Cx43 Gj. Cx43 gap junction channel open probability decreased to zero without reductions in the current amplitudes during external Ca2+/ionomycin perfusion. We conclude that Cx43 gap junctions are gated closed by a Ca2+/CaM-dependent mechanism involving the carboxyl-terminal quarter of the connexin CL domain. This study provides the first evidence of intrinsic differences in the Ca2+ regulatory properties of Cx43 and Cx40.

scholarly journals C-Terminal End of Aquaporin 0 Regulates Lens Gap Junction Channel Function

2019 ◽  
Vol 60 (7) ◽  
pp. 2525 ◽  
Author(s):  
Kulandaiappan Varadaraj ◽  
Junyuan Gao ◽  
Richard T. Mathias ◽  
Sindhu Kumari
Keyword(s):  
Gap Junction ◽  
Channel Function ◽  
Gap Junction Channel

scholarly journals CD4+ T lymphocyte subsets express connexin 43 and establish gap junction channel communication with macrophages in vitro

2007 ◽  
Vol 82 (3) ◽  
pp. 608-612 ◽  
Author(s):  
Alexandra Bermudez-Fajardo ◽  
Minna Ylihärsilä ◽  
W. Howard Evans ◽  
Andrew C. Newby ◽  
Ernesto Oviedo-Orta
Keyword(s):  
Gap Junction ◽  
T Lymphocyte ◽  
Connexin 43 ◽  
Lymphocyte Subsets ◽  
T Lymphocyte Subsets ◽  
Gap Junction Channel

scholarly journals The severity of mammary gland developmental defects is linked to the overall functional status of Cx43 as revealed by genetically modified mice

2012 ◽  
Vol 449 (2) ◽  
pp. 401-413 ◽  
Author(s):  
Michael K. G. Stewart ◽  
Xiang-Qun Gong ◽  
Kevin J. Barr ◽  
Donglin Bai ◽  
Glenn I. Fishman ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Gap Junction ◽  
Connexin 43 ◽  
Mammary Gland Development ◽  
Genetically Modified ◽  
Milk Ejection ◽  
Gap Junction Channel ◽  
Genetically Modified Mice ◽  
And Function ◽  
Gland Development

Genetically modified mice mimicking ODDD (oculodentodigital dysplasia), a disease characterized by reduced Cx43 (connexin 43)-mediated gap junctional intercellular communication, represent an in vivo model to assess the role of Cx43 in mammary gland development and function. We previously reported that severely compromised Cx43 function delayed mammary gland development and impaired milk ejection in mice that harboured a G60S Cx43 mutant, yet there are no reports of lactation defects in ODDD patients. To address this further, we obtained a second mouse model of ODDD expressing an I130T Cx43 mutant to assess whether a mutant with partial gap junction channel activity would be sufficient to retain mammary gland development and function. The results of the present study show that virgin Cx43I130T/+ mice exhibited a temporary delay in ductal elongation at 4 weeks. In addition, Cx43I130T/+ mice develop smaller mammary glands at parturition due to reduced cell proliferation despite similar overall gland architecture. Distinct from Cx43G60S/+ mice, Cx43I130T/+ mice adequately produce and deliver milk to pups, suggesting that milk ejection is unaffected. Thus the present study suggests that a loss-of-function mutant of Cx43 with partial gap junction channel coupling conductance results in a less severe mammary gland phenotype, which may partially explain the lack of reported lactation defects associated with ODDD patients.

Selective block of gap junction channel expression with connexin-specific antisense oligodeoxynucleotides

1994 ◽  
Vol 267 (5) ◽  
pp. C1371-C1380 ◽  
Author(s):  
L. K. Moore ◽  
J. M. Burt
Keyword(s):  
Gap Junction ◽  
Connexin 43 ◽  
Rat Aorta ◽  
Antisense Oligodeoxynucleotide ◽  
Gap Junction Channel ◽  
A7r5 Cells ◽  
Conduction Pathway ◽  
Channel Expression ◽  
A Cell ◽  
Channel Type

Gap junctions in vascular smooth muscle provide a cell-to-cell conduction pathway that may contribute to regulation and coordination of changes in vascular tone. A7r5 cells, a cell line derived from embryonic rat aorta, express connexin 43 (Cx43) and connexin 40 (Cx40). Gap junction channels with three distinct unitary conductances (70, 108, and 141 pS) were observed in these cells. Events of each channel type were equally common, with an approximate frequency of 30-35%; however, the frequency at which each channel type was observed in individual cell pairs ranged between 10 and 65%. Treatment of the cells for 24-72 h with an antisense oligodeoxynucleotide (ODN) to Cx43 reduced the relative frequency of the 108- and 141-pS channel events, whereas comparable treatment with antisense Cx40 ODN reduced the frequency at which 70-pS channel events were observed. The simplest explanation of these findings is that Cx43 forms the 108- and 141-pS channels, whereas Cx40 forms the 70-pS channels in A7r5 cells.

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