SCIENCE@home

Connexin43 Associated with an N-cadherin-containing Multiprotein Complex Is Required for Gap Junction Formation in NIH3T3 Cells*

C. Wei,Richard Francis,Xin Xu,C. Lo

Published 2005 in Journal of Biological Chemistry

ABSTRACT

Previous studies have indicated an intimate linkage between gap junction and adherens junction formation. It was suggested this could reflect the close membrane-membrane apposition required for junction formation. In NIH3T3 cells, we observed the colocalization of connexin43 (Cx43α1) gap junction protein with N-cadherin, p120, and other N-cadherin-associated proteins at regions of cell-cell contact. We also found that Cx43α1, N-cadherin, and N-cadherin-associated proteins were coimmunoprecipitated by antibodies to either Cx43α1, N-cadherin, or various N-cadherin-associated proteins. These findings suggest that Cx43α1 and N-cadherin are coassembled in a multiprotein complex containing various N-cadherin-associated proteins. Studies using siRNA knockdown indicated that cell surface expression of Cx43α1 required N-cadherin, and conversely, N-cadherin cell surface expression required Cx43α1. Pulse-chase labeling and cell surface biotinylation experiments indicated that in the absence of N-cadherin, Cx43α1 cell surface trafficking is blocked. Surprisingly, siRNA knockdown of p120, an N-cadherin-associated protein known to modulate cell surface turnover of N-cadherin, reduced N-cadherin cell surface expression without altering Cx43α1 expression. These observations suggest that in contrast to the coregulated cell surface trafficking of Cx43α1 and N-cadherin, N-cadherin turnover at the cell surface may be regulated independently of Cx43α1. Functional studies showed gap junctional communication is reduced and cell motility inhibited with N-cadherin or Cx43α1 knockdown, consistent with the observed loss of both gap junction and cadherin contacts with either knockdown. Overall, these studies indicate that the intracellular coassembly of connexin and cadherin is required for gap junction and adherens junction formation, a process that likely underlies the intimate association between gap junction and adherens junction formation.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-48 of 48 references · Page 1 of 1

CITED BY

Showing 1-100 of 226 citing papers · Page 1 of 3

123
Next