Assembly of Connexin43 into Gap Junctions Is Regulated Differentially by E-Cadherin and N-Cadherin in Rat Liver Epithelial Cells

Govindarajan, Rajgopal; Chakraborty, Souvik; Johnson, Kristen E.; Falk, Matthias M.; Wheelock, Margaret J.; Johnson, Keith R.; Mehta, Parmender P.

doi:10.1091/mbc.e10-05-0403

Cited by 48 publications

(61 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are a diverse number of proteins involved in the control of Cx43 internalization through multiple processes (Boassa et al, 2010;Gilleron et al, 2009;Gilleron et al, 2011;Girao et al, 2009;Govindarajan et al, 2010;Gumpert et al, 2008;Laird, 2010;Leithe et al, 2006;Leithe et al, 2009;Piehl et al, 2007;Auth et al, 2009). It appears that all of the identifi ed processes of internalization terminate in the lysosomal degradation of Cx43 (Guan and Ruch, 1996;Hesketh et al, 2010;Laing & Beyer, 1995;Laing et al, 1998;Laing et al, 1997;Leithe et al, 2006;Leithe et al, 2009;Lichtenstein et al, 2011;Murray et al, 1981;Naus et al, 1993;Qin et al, 2003;Sasaki & Garant, 1986;Simeckova et al, 2009;Thomas et al, 2003;Fong et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Immunofl uorescence (IF) and electron microscopy studies of connexins in endosomal structures (Murray et al, 1981;Naus et al, 1993;Sasaki & Garant, 1986) and IF microscopy evidence of connexins colocalized with endosomal markers such as 54 K. Cochrane et al EEA1, Rab5, and Rab7 (Boassa et al, 2010;Gilleron et al, 2008;Govindarajan et al, 2010;Leithe et al, 2006;Leithe et al, 2009;Segretain et al, 2003) suggest that connexins are internalized from the plasma membrane by endocytic mechanisms. This is also supported by an evidence that the knockdown of proteins required for clathrin-mediated endocytosis such as clathrin, dynamin2, adapter protein complex-2 (AP-2), and Disabled-2 (Dab2) inhibited the internalization of connexin43 (Cx43) (Gilleron et al, 2011;Gumpert et al, 2008;Piehl et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The connexin43-interacting protein, CIP85, mediates the internalization of connexin43 from the plasma membrane

Cochrane

Lau

2013

Cell Communication & Adhesion

View full text Add to dashboard Cite

CIP85 was previously identifi ed as a connexin43 (Cx43)-interacting protein that is ubiquitously expressed in multiple mammalian tissues and cell types. The interaction between the SH3 domain of CIP85 and a proline-rich region of Cx43 has previously been associated with an increased rate of Cx43 turnover through lysosomal mechanisms. This report presents biochemical and immunofl uorescence evidence that overexpression of CIP85 reduced the presence of Cx43 in gap junction plaques at the plasma membrane. Furthermore, this effect was dependent upon the interaction of CIP85 with Cx43 at the plasma membrane. These results indicate that CIP85 increases Cx43 turnover by accelerating the internalization of Cx43 from the plasma membrane. CIP85 was also observed to interact with clathrin, which suggested a role for CIP85 in the clathrin-mediated internalization of Cx43.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The connexin43-interacting protein, CIP85, mediates the internalization of connexin43 from the plasma membrane

Cochrane

Lau

2013

Cell Communication & Adhesion

View full text Add to dashboard Cite

show abstract

“…Antibodies and Immunostaining-Rabbit polyclonal and mouse monoclonal antibodies against Cx32 and mouse anti-␤-catenin, and rabbit anti-␤-actin have been described previously (18,19,21). We also used rabbit polyclonal antibodies raised against the carboxyl tail (Sigma; C-3470) and the cytoplasmic loop of Cx32 (Sigma, C-3595).…”

Section: Methodsmentioning

confidence: 99%

“…Detergent Extraction and Western Blot Analysis-BxPC3 (3 ϫ 10 6 ) and LNCaP (2 ϫ 10 6 ) cells, seeded in replicate 10-cm dishes in 10 ml of complete medium, were grown for 72 h. The procedures for cell lysis, detergent-solubility assay with 1% Triton X-100 (TX100) and Western blot analysis have been described previously (18,19,21). Normalization was based on equal cell number for the analysis of detergent-soluble and -insoluble fractions by SDS-PAGE analysis of cell lysates.…”

Section: Methodsmentioning

confidence: 99%

The Carboxyl Tail of Connexin32 Regulates Gap Junction Assembly in Human Prostate and Pancreatic Cancer Cells

Katoch

Mitra

Ray

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

“…To produce recombinant retrovirus for infection of target cells, amphotropic PTi67 cells were infected with the transiently produced recombinant retrovirus from EcoPack and selected in G418 (400 μg/ml). The recombinant retrovirus produced from the pooled polyclonal cultures of PTi67 cells was assayed for the virus titer by colony forming units as described [17][18][19][20][21][22].…”

Section: B) Prepare Recombinant Retrovirus Containing E-cadherin-camentioning

confidence: 99%

Connexins and Cadherin Cross-talk in the Pathogenesis of Prostate Cancer

Johnson¹,

Mehta²

2013

Self Cite

View full text Add to dashboard Cite

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTGap junctions are ensembles of cell-cell channels that are formed by proteins called connexins. They permit the passage of small molecules between cells and maintain homeostasis. We have found that connexin32 and connexin43 are assembled into gap junctions in normal prostate but remain intracellular in prostate tumors. Our studies showed that the expression of anti-metastatic E-cadherin facilitated gap junction assembly whereas the expression of pro-invasive N-cadherin disrupted assembly. We hypothesized that gap junction assembly was the downstream target of signaling initiated by cadherins. We had proposed 2 specific aims to test this hypothesis. The proposed studies of Aim 1 were to determine how E-cadherin mediated cell-cell adhesion controlled gap junction assembly in prostate cancer cells whereas of aim 2 were to determine the molecular mechanisms by which E-cadherin and N-cadherin modulate gap junction assembly differentially. We have identified key motifs that regulate the endocytosis of connexin43 and connexin32 by clathrin-mediated pathway. Endocytosis of connexin43 is regulated through phosphorylation of serine 279 and 282 via clathrin-mediated pathway whereas that of connexin32 is regulated by three dileucinelike motifs in its cytoplasmic tail. Expression of mutant connexin32, in which the two dileucine-like motifs are mutated, results in the formation of large gap junctions. Finally, we have identified a new post-translational modification of 120-catenin that affects cadherin-connexin cross talk.

show abstract

Assembly of Connexin43 into Gap Junctions Is Regulated Differentially by E-Cadherin and N-Cadherin in Rat Liver Epithelial Cells

Abstract: E-cadherin and N-cadherin affect the assembly of connexin43 into gap junctions differentially. N-cadherin disrupts assembly by triggering endocytosis of connexin43, whereas E-cadherin facilitates the assembly.

Cited by 48 publications

References 85 publications

The connexin43-interacting protein, CIP85, mediates the internalization of connexin43 from the plasma membrane

The connexin43-interacting protein, CIP85, mediates the internalization of connexin43 from the plasma membrane

The Carboxyl Tail of Connexin32 Regulates Gap Junction Assembly in Human Prostate and Pancreatic Cancer Cells

Connexins and Cadherin Cross-talk in the Pathogenesis of Prostate Cancer

Contact Info

Product

Resources

About