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Updated: Jun 2, 2026

Functional Assessment of Intestinal Tight Junction Barrier and Ion Permeability in Native Tissue by Ussing Chamber Technique
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Functional Assessment of Intestinal Tight Junction Barrier and Ion Permeability in Native Tissue by Ussing Chamber Technique

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Occludin S408 phosphorylation regulates tight junction protein interactions and barrier function

David R Raleigh1, Devin M Boe, Dan Yu

  • 1Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.

The Journal of Cell Biology
|May 4, 2011
PubMed

Insights

Inhibition of occludin S408 phosphorylation by CK2 enhances tight junction barrier function. This involves dynamic remodeling of key proteins, potentially offering therapeutic avenues for inflammatory conditions.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • The C-terminal tail of occludin, a tight junction protein, is extensively phosphorylated, but the functional roles of specific phosphorylation sites remain largely unknown.
  • Understanding these roles is crucial for deciphering tight junction regulation and its impact on barrier function.

Purpose of the Study:

  • To investigate the functional significance of occludin S408 phosphorylation mediated by Casein Kinase 2 (CK2).
  • To elucidate the molecular mechanisms by which occludin S408 phosphorylation influences tight junction protein dynamics and interactions.

Main Methods:

  • Utilized biochemical and biophysical techniques to assess the impact of CK2 inhibition on occludin phosphorylation and tight junction integrity.
  • Employed protein exchange assays and co-immunoprecipitation to analyze the dynamic behavior and binding interactions of tight junction proteins.
  • Investigated the effects of CK2 inhibition on IL-13-induced barrier dysfunction.

Main Results:

  • Inhibition of CK2-mediated occludin S408 phosphorylation significantly increased transepithelial resistance by reducing cation flux.
  • S408 dephosphorylation altered the dynamic exchange of occludin, ZO-1, claudin-1, and claudin-2, leading to a convergence of their mobile fractions.
  • Specific ZO-1 domains were essential for increased claudin-2 exchange, indicating the formation of a phosphorylation-sensitive complex.
  • CK2 inhibition reversed IL-13-induced barrier loss, highlighting the role of occludin S408 in inflammatory responses.

Conclusions:

  • Occludin S408 dephosphorylation is a key regulator of paracellular permeability through modulation of tight junction protein dynamics and interactions.
  • This mechanism involves remodeling of protein complexes containing occludin, ZO-1, and specific claudins (claudin-1, claudin-2).
  • Targeting occludin S408 phosphorylation may offer a therapeutic strategy for managing inflammation-associated barrier dysfunction.

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