Plakoglobin supresses keratinocyte motility through both cell-cell adhesion-dependent and -independent mechanisms

Taofei Yin, Spiro Getsios, Reto Caldelari, Andrew P. Kowakzyk, Eliane J. Müller, Jonathan C R Jones, Kathleen J. Green*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Plakoglobin (PG) is a member of the Armadillo family of adhesion/signaling proteins and has been shown to play a critical role in the organization of desmosomes and tissue integrity. Because dissolution of intercellular junctions is frequently an initial step in the onset of epithelial cell migration, we examined whether loss of PG promotes cell motility by compromising adhesive strength. Keratinocyte cultures established from PG-/- mice exhibited weakened adhesion and increased motility in transwell migration assays; both were restored by reintroducing PG through adenoviral infection. Interestingly, single PG-/- cells also exhibited increased motility, which was suppressed by reintroducing PG, but not the closely related β-catenin. Whereas both N- and C-terminally truncated PG deletion mutants restored adhesion, only N-terminally deleted PG, but not C-terminally deleted PG, suppressed single-cell migration. Furthermore, both the chemical inhibitor PP2 and dominant-negative Src tyrosine kinase inhibited single-cell motility in PG-/- cellS, whereas constitutively active Src overcame the inhibitory effect of PG. These data demonstrate that PG strengthens adhesion and suppresses motility in mouse keratinocytes, through both intercellular adhesion-dependent and -independent mechanisms, the latter of which may involve suppression of Src signaling through a mechanism requiring the PG C terminus.

Original languageEnglish (US)
Pages (from-to)5420-5425
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number15
DOIs
StatePublished - Apr 12 2005

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Plakoglobin supresses keratinocyte motility through both cell-cell adhesion-dependent and -independent mechanisms'. Together they form a unique fingerprint.

Cite this