Connexins: a connection with the skin

Richard, G.

doi:10.1034/j.1600-0625.2000.009002077.x

Cited by 162 publications

(119 citation statements)

References 92 publications

(160 reference statements)

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…To date, nine different connexins have been described in the murine epidermis (reviewed by Richard, 2000a). The connexin expression pattern in rodents is altered during embryogenesis and after birth (Risek et al, 1992;Choudry et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…In the epidermis of adult mice, Cx43 and Cx40 are expressed in the basal layer and Cx43 and Cx31 are expressed in the spinous layer. In the granulous layer, Cx43 expression no longer occurs, so that besides weak expression of Cx26, only Cx31 appears in this layer (Kamibayashi et al, 1993;Butterweck et al, 1994) (reviewed by Richard, 2000a). Transcripts of Cx30, Cx30.3, Cx31.1 and Cx57 have been found in mouse epidermis but the epidermal expression pattern of the corresponding proteins has not yet been analyzed (Manthey et al, 1999;Hennemann et al, 1992;Dahl et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Altered connexin expression and wound healing in the epidermis of connexin-deficient mice

Kretz¹,

Euwens²,

Hombach³

et al. 2003

Journal of Cell Science

139

151

View full text Add to dashboard Cite

To analyze the effect of connexin loss on the repair of wounded tail skin,we have studied the following transgenic mouse mutants: connexin30–/–, connexin31–/– and connexin43Cre-ER(T)/fl (for inducible deletion of the connexin43 coding region). Connexin43 and connexin31 are expressed in the basal and spinous layers of wild-type epidermis, whereas connexin31 and small amounts of connexin30, as well as connexin26 proteins,were found in the granulous layer. Connexin43 was downregulated in connexin31-deficient mice, whereas mice with reduced connexin43 exhibited an upregulation of connexin30. During wound healing, connexin30 and connexin26 proteins were upregulated in all epidermal layers, whereas connexin43 and connexin31 protein expression were downregulated. In connexin31–/– mice, reduced levels of connexin30 protein were observed on days 1 and 2 after wounding. The closure of epidermal wounds in mice with decreased amounts of connexin43 protein occurred one day earlier. Under these conditions the expression profiles of connexin30 and connexin31 were also temporarily shifted by one day. Furthermore, dye transfer between keratinocytes in skin sections from connexin43-deficient mice was decreased by 40%. These results suggest that downregulation of connexin43 appears to be a prerequisite for the coordinated proliferation and mobilization of keratinocytes during wound healing.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Altered connexin expression and wound healing in the epidermis of connexin-deficient mice

Kretz¹,

Euwens²,

Hombach³

et al. 2003

Journal of Cell Science

139

151

View full text Add to dashboard Cite

show abstract

“…he well coordinated functioning of cells within tissues is ensured by multiple mechanisms, including the direct exchange of ions, second messengers, and other metabolites through connexin channels, clustered at gap junctions (1,2). These channels connect almost all types of vertebrate cells, including those of pancreatic islets (3).…”

mentioning

confidence: 99%

Connexin 36 Controls Synchronization of Ca2+ Oscillations and Insulin Secretion in MIN6 Cells

et al. 2003

View full text Add to dashboard Cite

1Cx36 is the predominant connexin isoform expressed by pancreatic ␤-cells. However, little is known about the role of this protein in the functioning of insulin-secreting cells. To address this question, we searched for a cell line expressing Cx36 and having glucose-induced insulin secretion comparable to that of primary ␤-cells. T he well coordinated functioning of cells within tissues is ensured by multiple mechanisms, including the direct exchange of ions, second messengers, and other metabolites through connexin channels, clustered at gap junctions (1,2). These channels connect almost all types of vertebrate cells, including those of pancreatic islets (3). Previous studies suggest that connexin-mediated communication between ␤-cells is required for the control of insulin secretion. Thus, glucose stimulation of single ␤-cells is reduced compared with that of cell clusters (4), pharmacological blockade of gap junction channels markedly decreases insulin release (5), and transgenic mice whose ␤-cells express Cx32 show altered insulin secretion in response to glucose (6). While these findings provide evidence that connexin-dependent communication contributes to the control of insulin release, they do not specifically address the function of native connexins expressed by pancreatic islet cells.We recently found that Cx36 is the predominant isoform expressed by ␤-cells (7). As yet, however, the specific role of this somewhat unusual connexin isoform (8,9) and, in particular, its possible contribution to insulin secretion have not been investigated. Moreover, no data are available to show how connexin-mediated signaling may influence ␤-cell function even though gap junctions have been implicated in the synchronization of [Ca 2ϩ ] i oscillations in ␤-cells (10 -13).To address these questions, we screened MIN6 cells, which, unlike some other cell lines, retain glucose-induced insulin secretion and express Cx36 like primary ␤-cells (14 -19). We decreased Cx36 expression via the stable transfection of an antisense construct. Here, we show that the loss of Cx36 resulted in impaired electrical coupling, desynchronization of [Ca 2ϩ ] i oscillations, and altered insulin release of MIN6 cells. These results support the hypothesis that Cx36 plays a critical role in glucoseinduced insulin secretion. RESEARCH DESIGN AND METHODSCell lines and tissues. RIN2A (14), INS1 (15), and HIT cells (16) were cultured in RPMI-1640 medium, whereas ␤TC3 (17) and MIN6 cells (18) were cultured in Dulbecco's modified Eagle's medium as indicated in the original reports. Control tissues were obtained from OFA rats (olfactory bulb) or C57BL/6 mice (liver and heart), which were frozen in liquid nitrogen and stored at Ϫ80°C until use. RNA analysis. Samples of total RNA were extracted, reverse-transcribed, and amplified as previously described (7). To detect native Cx36, we amplified either a 980-bp or a 559-bp fragment, using the oligonucleotide pairs 5Ј-CACAGCGATGGGGGAATGGA-3Ј/5Ј-TGCCCTTTCACACATAGGCA-3Ј and 5Ј-GAGCCCAGGCCAAGAGGAAGTC-3Ј/5Ј-GG...

show abstract

“…Intercellular channels result from the association of two half-channels named connexons, which are contributed to separately by each of two adjacent cells. Each connexon is an assembly of membrane proteins named connexins, which are encoded by a gene family consisting of at least 20 members (5,6).…”

mentioning

confidence: 99%

Critical Role of the Transcriptional Repressor Neuron-restrictive Silencer Factor in the Specific Control of Connexin36 in Insulin-producing Cell Lines

Martín

Tawadros

Meylan

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Adjacent cells share ions, second messengers, small metabolites, and signaling molecules with a weight as high as 1000 Da (1) through intercellular channels that form gap junctions. This type of intercellular communication permits coordinated cellular activity and allows cells to review the functional state of their neighbors, a critical feature for the homeostasis of multicellular organisms (1-4). Intercellular channels result from the association of two half-channels named connexons, which are contributed to separately by each of two adjacent cells. Each connexon is an assembly of membrane proteins named connexins, which are encoded by a gene family consisting of at least 20 members (5, 6).It has been reported that Cx36 1 is the predominantly expressed connexin in rodent neuronal cells (7-9). Immunogold labeling using freeze-fracture replicas have shown that Cx36 was found only in neurons (10) and indicate that the specific expression of connexins by the different cell types of the nervous system may define separate pathways for neuronal versus glial gap junction communication (10 -12). We recently found that Cx36 is the predominant if not the sole connexin isoform expressed in insulin-producing ␤-cells of rat and mouse pancreatic islets (13,14). Recently, Cx36 content was modified in insulin-secreting cells by using an adenoviral gene transfer approach (15) or a lentivirus-mediated transduction of cx36 cDNA (16) in order to evaluate the contribution of Cx36 in the control of insulin secretion and content. These experiments have demonstrated that tight levels of Cx36 are crucial for proper function of insulin-producing cells. Moreover, stably transfected insulin-secreting MIN6 cells with a cx36 antisense cDNA impaired the synchronization of glucose-induced Ca( 2ϩ ) oscillations and insulin secretion in response to glucose (17). These data provided evidence that proper storage of insulin as well as the regulation of insulin release required that the levels of Cx36 be maintained within native values.The objective of the present study was to characterize the mechanisms of cell-specific expression of Cx36. The presence of several gene transcripts in pancreatic ␤-cells and neuronal cells was correlated with the absence in these cell types of a transcription factor named NRSF/REST (neuron-restrictive silencer factor/repressor element silencing transcription factor) (18). NRSF/REST binds to a 21-bp cis element named neuronal restrictive silencer element (NRSE). Through this NRSE, NRSF/REST has been identified as a negative regulatory system that silences neuronal gene expression in non-neuronal tissues, neuronal precursor cells, and certain differentiated

show abstract

Connexins: a connection with the skin

Cited by 162 publications

References 92 publications

Altered connexin expression and wound healing in the epidermis of connexin-deficient mice

Altered connexin expression and wound healing in the epidermis of connexin-deficient mice

Connexin 36 Controls Synchronization of Ca2+ Oscillations and Insulin Secretion in MIN6 Cells

Critical Role of the Transcriptional Repressor Neuron-restrictive Silencer Factor in the Specific Control of Connexin36 in Insulin-producing Cell Lines

Contact Info

Product

Resources

About