Cell coupling mediated by connexin 26 selectively contributes to reduced adhesivity and increased migration

Srikanth R. Polusani, Edward A. Kalmykov, Anjana Chandrasekhar, Shoshanna N. Zucker, Bruce J. Nicholson

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Gap junction proteins (connexins) have crucial effects on cell motility in many systems, from migration of neural crest cells to promotion of metastatic invasiveness. Here, we show that expression of Cx26 (also known as GJB2) in HeLa cells specifically enhances cell motility in scrape wounding and sparse culture models. This effect is dependent on gap junction channels and is isotype specific [Cx26 enhances motility, whereas Cx43 (also known as GJA1) does not and Cx32 (also known as GJB1) has an intermediate effect]. The increased motility is associated with reduced cell adhesiveness, caused by loss of N-cadherin protein and RNA at the wound edge. This in turn causes a redistribution of N-cadherin-binding proteins (p120 catenin and β- catenin) to the cytosol and nucleus, respectively. The former activates Rac-1, which mediates cytoskeletal rearrangements needed for filopod extension. The latter is associated with increased expression of urokinase plasminogen activating receptor (an activator of extracellular proteases) and secretion of extracellular matrix components like collagen. Although these effects were dependent on Cx26-mediated coupling of the cells, they are not mediated by the same signal (i.e. cAMP) through which Cx26 has been shown to suppress proliferation in the same system.

Original languageEnglish (US)
Pages (from-to)4399-4410
Number of pages12
JournalJournal of cell science
Volume129
Issue number23
DOIs
StatePublished - 2016

Keywords

  • Cell adhesion
  • Cell motility
  • Connexin
  • Gap junction

ASJC Scopus subject areas

  • Cell Biology

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