Interaction of arsenic with gap junction protein connexin 43 alters gap junctional intercellular communication

Abstract The aim of this study was to investigate whether fine and ultrafine carbon black (fC and ufC), and fine and ultrafine silica (fS, ufS) particles affect gap junctional intercellular communication (GJIC) in rat lung epithelial cells. Exposure of cells to subcytotoxic doses of ufC, fS and ufS resulted in a 63%, 59% and 77% reduction of GJIC, respectively, as determined in a dye transfer assay. In contrast to ufC, fC did not significantly alter GJIC. Changes in subcellular localization of the major gap junction protein in RLE cells, connexin-43 (Cx43), and of β-catenin were observed in cells exposed to ufC, fS or ufS. The loss of GJIC was counteracted by N-acetyl cysteine and was largely prevented by specific inhibitors of epidermal growth factor receptor-dependent signaling, pointing to the crucial role of two known major mediators of nanoparticle action, namely reactive oxygen species and membrane-receptor signaling, in particle-induced modulation of GJIC.

Download Full-text

Differentiation of human fetal osteoblastic cells and gap junctional intercellular communication

AJP Cell Physiology ◽

10.1152/ajpcell.2000.278.2.c315 ◽

2000 ◽

Vol 278 (2) ◽

pp. C315-C322 ◽

Cited By ~ 88

Author(s):

Henry J. Donahue ◽

Zhongyong Li ◽

Zhiyi Zhou ◽

Clare E. Yellowley

Keyword(s):

Alkaline Phosphatase ◽

Gap Junction ◽

Phosphatase Activity ◽

Alkaline Phosphatase Activity ◽

Intercellular Communication ◽

Connexin 43 ◽

Osteoblastic Cells ◽

Gap Junctional Intercellular Communication ◽

Osteoblastic Cell Line ◽

Gap Junctional

Gap junctional channels facilitate intercellular communication and in doing so may contribute to cellular differentiation. To test this hypothesis, we examined gap junction expression and function in a temperature-sensitive human fetal osteoblastic cell line (hFOB 1.19) that when cultured at 37°C proliferates rapidly but when cultured at 39.5°C proliferates slowly and displays increased alkaline phosphatase activity and osteocalcin synthesis. We found that hFOB 1.19 cells express abundant connexin 43 (Cx43) protein and mRNA. In contrast, Cx45 mRNA was expressed to a lesser degree, and Cx26 and Cx32 mRNA were not detected. Culturing hFOB 1.19 cells at 39.5°C, relative to 37°C, inhibited proliferation, increased Cx43 mRNA and protein expression, and increased gap junctional intercellular communication (GJIC). Blocking GJIC with 18α-glycyrrhetinic acid prevented the increase in alkaline phosphatase activity resulting from culture at 39.5°C but did not affect osteocalcin levels. These results suggest that gap junction function and expression parallel osteoblastic differentiation and contribute to the expression of alkaline phosphatase activity, a marker for fully differentiated osteoblastic cells.

Download Full-text

Shapes of astrocyte networks in the juvenile brain

Neuron Glia Biology ◽

10.1017/s1740925x06000081 ◽

2006 ◽

Vol 2 (1) ◽

pp. 3-14 ◽

Cited By ~ 65

Author(s):

VANESSA HOUADES ◽

NATHALIE ROUACH ◽

PASCAL EZAN ◽

FRANK KIRCHHOFF ◽

ANNETTE KOULAKOFF ◽

...

Keyword(s):

Gap Junction ◽

Brain Function ◽

Connexin 43 ◽

Gap Junctional Communication ◽

Junctional Communication ◽

Junction Protein ◽

Gap Junction Protein ◽

High Level ◽

Gap Junctional ◽

Neuronal Compartments

The high level of intercellular communication mediated by gap junctions between astrocytes indicates that, besides individual astrocytic domains, a second level of organization might exist for these glial cells as they form communicating networks. Therefore, the contribution of astrocytes to brain function should also be considered to result from coordinated groups of cells. To evaluate the shape and extent of these networks we have studied the expression of connexin 43, a major gap junction protein in astrocytes, and the intercellular diffusion of gap junction tracers in two structures of the developing brain, the hippocampus and the cerebral cortex. We report that the shape of astrocytic networks depends on their location within neuronal compartments in a defined brain structure. Interestingly, not all astrocytes are coupled, which indicates that connections within these networks are restricted. As gap junctional communication in astrocytes is reported to contribute to several glial functions, differences in the shape of astrocytic networks might have consequences on neuronal activity and survival.

Download Full-text

A germline-specific gap junction protein required for survival of differentiating early germ cells

Development ◽

10.1242/dev.129.10.2529 ◽

2002 ◽

Vol 129 (10) ◽

pp. 2529-2539 ◽

Cited By ~ 6

Author(s):

Salli I. Tazuke ◽

Cordula Schulz ◽

Lilach Gilboa ◽

Mignon Fogarty ◽

Anthony P. Mahowald ◽

...

Keyword(s):

Germ Cell ◽

Gap Junction ◽

Germ Cells ◽

Somatic Cells ◽

Gap Junctional Intercellular Communication ◽

Germ Cell Differentiation ◽

Junction Protein ◽

Gap Junction Protein ◽

Zero Population Growth ◽

Gap Junctional

Germ cells require intimate associations and signals from the surrounding somatic cells throughout gametogenesis. The zero population growth (zpg) locus of Drosophila encodes a germline-specific gap junction protein, Innexin 4, that is required for survival of differentiating early germ cells during gametogenesis in both sexes. Animals with a null mutation in zpg are viable but sterile and have tiny gonads. Adult zpg-null gonads contain small numbers of early germ cells, resembling stem cells or early spermatogonia or oogonia, but lack later stages of germ cell differentiation. In the male, Zpg protein localizes to the surface of spermatogonia, primarily on the sides adjacent to the somatic cyst cells. In the female, Zpg protein localizes to germ cell surfaces, both those adjacent to surrounding somatic cells and those adjacent to other germ cells. We propose that Zpg-containing gap junctional hemichannels in the germ cell plasma membrane may connect with hemichannels made of other innexin isoforms on adjacent somatic cells. Gap junctional intercellular communication via these channels may mediate passage of crucial small molecules or signals between germline and somatic support cells required for survival and differentiation of early germ cells in both sexes.

Download Full-text

Regulation of connexin 43-mediated gap junctional intercellular communication by Ca2+ in mouse epidermal cells is controlled by E-cadherin.

The Journal of Cell Biology ◽

10.1083/jcb.114.3.545 ◽

1991 ◽

Vol 114 (3) ◽

pp. 545-555 ◽

Cited By ~ 243

Author(s):

W M Jongen ◽

D J Fitzgerald ◽

M Asamoto ◽

C Piccoli ◽

T J Slaga ◽

...

Keyword(s):

Connexin 43 ◽

Epidermal Cells ◽

Cell Contact ◽

Gap Junctional Intercellular Communication ◽

Calcium Dependent ◽

Junction Protein ◽

Dependent Cell ◽

Gap Junction Protein ◽

Gap Junctional ◽

E Cadherin

Gap junctional intercellular communication (GJIC) of cultured mouse epidermal cells is mediated by a gap junction protein, connexin 43, and is dependent on the calcium concentration in the medium, with higher GJIC in a high-calcium (1.2 mM) medium. In several mouse epidermal cell lines, we found a good correlation between the level of GJIC and that of immunohistochemical staining of E-cadherin, a calcium-dependent cell adhesion molecule, at cell-cell contact areas. The variant cell line P3/22 showed both low GJIC and E-cadherin protein expression in low- and high-Ca2+ media. P3/22 cells showed very low E-cadherin mRNA expression. To test directly whether E-cadherin is involved in the Ca(2+)-dependent regulation of GJIC, we transfected the E-cadherin expression vector into P3/22 cells and obtained several stable clones which expressed high levels of E-cadherin mRNA. All transfectants expressed E-cadherin molecules at cell-cell contact areas in a calcium-dependent manner. GJIC was also observed in these transfectants and was calcium dependent. These results suggest that Ca(2+)-dependent regulation of GJIC in mouse epidermal cells is directly controlled by a calcium-dependent cell adhesion molecule, E-cadherin. Furthermore, several lines of evidence suggest that GJIC control by E-cadherin involves posttranslational regulation (assembly and/or function) of the gap junction protein connexin 43.

Download Full-text

The atypical chemokine receptor 3 interacts with Connexin 43 inhibiting astrocytic gap junctional intercellular communication

Nature Communications ◽

10.1038/s41467-020-18634-y ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Amos Fumagalli ◽

Joyce Heuninck ◽

Anne Pizzoccaro ◽

Enora Moutin ◽

Joyce Koenen ◽

...

Keyword(s):

Mouse Brain ◽

Chemokine Receptor ◽

Intercellular Communication ◽

Intracellular Signaling ◽

Connexin 43 ◽

Gap Junctional Intercellular Communication ◽

Functional Link ◽

Embryonic Mouse ◽

Junction Protein ◽

Gap Junctional

Abstract The atypical chemokine receptor 3 (ACKR3) plays a pivotal role in directing the migration of various cellular populations and its over-expression in tumors promotes cell proliferation and invasiveness. The intracellular signaling pathways transducing ACKR3-dependent effects remain poorly characterized, an issue we addressed by identifying the interactome of ACKR3. Here, we report that recombinant ACKR3 expressed in HEK293T cells recruits the gap junction protein Connexin 43 (Cx43). Cx43 and ACKR3 are co-expressed in mouse brain astrocytes and human glioblastoma cells and form a complex in embryonic mouse brain. Functional in vitro studies show enhanced ACKR3 interaction with Cx43 upon ACKR3 agonist stimulation. Furthermore, ACKR3 activation promotes β-arrestin2- and dynamin-dependent Cx43 internalization to inhibit gap junctional intercellular communication in primary astrocytes. These results demonstrate a functional link between ACKR3 and gap junctions that might be of pathophysiological relevance.

Download Full-text

Faculty Opinions recommendation of Gap junction protein connexin-43 interacts directly with microtubules.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1000542.9460 ◽

2001 ◽

Author(s):

Nalin Kumar

Keyword(s):

Gap Junction ◽

Connexin 43 ◽

Junction Protein ◽

Gap Junction Protein

Download Full-text

Faculty Opinions recommendation of Gap junction protein Connexin-43 is a direct transcriptional regulator of N-cadherin in vivo.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734059662.793568874 ◽

2019 ◽

Author(s):

Kathleen J Green

Keyword(s):

Gap Junction ◽

Connexin 43 ◽

Transcriptional Regulator ◽

Junction Protein ◽

Gap Junction Protein

Download Full-text

Doxorubicin induces EGF receptor-dependent downregulation of gap junctional intercellular communication in rat liver epithelial cells

Biological Chemistry ◽

10.1515/bc.2005.027 ◽

2005 ◽

Vol 386 (3) ◽

pp. 217-223 ◽

Cited By ~ 19

Author(s):

Kotb Abdelmohsen ◽

Claudia von Montfort ◽

Dominik Stuhlmann ◽

P. Arne Gerber ◽

Ulrich K.M. Decking ◽

...

Keyword(s):

Epithelial Cells ◽

Rat Liver ◽

Intercellular Communication ◽

Connexin 43 ◽

Egf Receptor ◽

Gap Junctional Intercellular Communication ◽

Erk Activation ◽

Liver Epithelial Cells ◽

Rat Liver Epithelial Cells ◽

Gap Junctional

Abstract Exposure of rat liver epithelial cells to doxorubicin, an anthraquinone derivative widely employed in cancer chemotherapy, led to a dose-dependent decrease in gap junctional intercellular communication (GJC). Gap junctions are clusters of inter-cellular channels consisting of connexins, the major connexin in the cells used being connexin-43 (Cx43). Doxorubicin-induced loss of GJC was mediated by activation of extracellular signal-regulated kinase (ERK)-1 and ERK-2, as demonstrated using inhibitors of ERK activation. Furthermore, activation of the epidermal growth factor (EGF) receptor by doxorubicin was responsible for ERK activation and the subsequent attenuation of GJC. Inhibition of GJC, however, was not by direct phosphorylation of Cx43 by ERK-1/2, whereas menadione, a 1,4-naphthoquinone derivative that was previously demonstrated to activate the same EGF receptor-dependent pathway as doxorubicin, resulting in downregulation of GJC, caused strong phos-phorylation of Cx43 at serines 279 and 282. Thus, ERK-dependent downregulation of GJC upon exposure to quinones may occur both by direct phosphorylation of Cx43 and in a phosphorylation-independent manner.

Download Full-text