Regulation of epithelial tight junction assembly and disassembly by AMP-activated protein kinase Academic Article uri icon

Overview

MeSH Major

  • Epithelial Cells
  • Multienzyme Complexes
  • Protein-Serine-Threonine Kinases
  • Tight Junctions

abstract

  • AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that plays an important role in maintaining cellular energy balance. The activity of AMPK is modulated both by the cellular AMP-to-ATP ratio and by upstream kinases. Recently, AMPK was shown to be phosphorylated and activated by LKB1, a protein kinase that plays a conserved role in epithelial polarity regulation in mammals and Drosophila. Here, we investigate the involvement of AMPK in the regulation of epithelial tight junction assembly and cell polarization in MDCK cells. We show that the level of AMPK phosphorylation increases during calcium-induced tight junction assembly and cell polarization and that this increase depends on the kinase activity of LKB1. Expression of a kinase-dead mutant of AMPK inhibits tight junction assembly as indicated by measurement of transepithelial resistance and analysis of ZO-1 localization to the tight junction after calcium switch. Conversely, 5-aminoimidizole-4-carboxamide riboside, an activator of AMPK, promotes transepithelial resistance development and tight junction assembly upon calcium switch. Furthermore, 5-aminoimidizole-4-carboxamide riboside partially protects the tight junctions from disassembly induced by calcium depletion. These results support an important role of AMPK in the regulation of epithelial tight junction assembly and disassembly and suggest an intriguing link between cellular energy status and tight junction function.

publication date

  • January 16, 2007

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1783397

Digital Object Identifier (DOI)

  • 10.1073/pnas.0610157104

PubMed ID

  • 17204563

Additional Document Info

start page

  • 819

end page

  • 22

volume

  • 104

number

  • 3