Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure

Le Shen, Eric D. Black, Edwina D. Witkowski, Wayne I. Lencer, Vince Guerriero, Eveline E. Schneeberger, Jerrold R. Turner

Research output: Contribution to journalArticle

290 Scopus citations

Abstract

Epithelial tight junctions form a barrier against passive paracellular flux. This barrier is regulated by complex physiologic and pathophysiologic signals that acutely fine-tune tight junction permeability. Although actomyosin contraction and myosin light chain phosphorylation are clearly involved in some forms of tight junction regulation, the contributions of other signaling events and the role of myosin light chain phosphorylation in this response are poorly understood. Here we ask if activation of myosin light chain kinase alone is sufficient to induce downstream tight junction regulation. We use a confluent polarized intestinal epithelial cell model system in which constitutively active myosin light chain kinase, tMLCK, is expressed using an inducible promoter. tMLCK expression increases myosin light chain phosphorylation, reorganizes perijunctional F-actin, and increases tight junction permeability. TJ proteins ZO-1 and occludin are markedly redistributed, morphologically and biochemically, but effects on claudin-1 and claudin-2 are limited. tMLCK inhibition prevents changes in barrier function and tight junction organization induced by tMLCK expression, suggesting that these events both require myosin light chain phosphorylation. We conclude that myosin light chain phosphorylation alone is sufficient to induce tight junction regulation and provide new insights into the molecular mechanisms that mediate this regulation.

Original languageEnglish (US)
Pages (from-to)2095-2106
Number of pages12
JournalJournal of Cell Science
Volume119
Issue number10
DOIs
StatePublished - May 15 2006

Keywords

  • Barrier
  • Claudin
  • Epithelial
  • Occludin
  • ZO-1

ASJC Scopus subject areas

  • Cell Biology

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    Shen, L., Black, E. D., Witkowski, E. D., Lencer, W. I., Guerriero, V., Schneeberger, E. E., & Turner, J. R. (2006). Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure. Journal of Cell Science, 119(10), 2095-2106. https://doi.org/10.1242/jcs.02915