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Updated: Jul 12, 2025

Functional Assessment of Intestinal Tight Junction Barrier and Ion Permeability in Native Tissue by Ussing Chamber Technique
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PATJ inhibits histone deacetylase 7 to control tight junction formation and cell polarity

Julia Fiedler1, Thomas Moennig1, Johanna H Hinrichs1

  • 1Department of Medical Cell Biology, Medical Clinic D, University Hospital of Münster, Albert-Schweitzer-Campus 1-A14, 48149, Münster, Germany.

Cellular and Molecular Life Sciences : CMLS
|October 25, 2023
PubMed

Insights

The protein PATJ regulates epithelial cell polarity and tight junction formation by inhibiting HDAC7. This finding reveals a new mechanism for controlling cell structure and function.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Epithelial Biology

Background:

  • The protein PATJ is crucial for maintaining epithelial cell polarity and tight junctions.
  • The precise molecular mechanisms underlying PATJ's function remain largely unknown.

Purpose of the Study:

  • To elucidate the molecular mechanism by which PATJ regulates epithelial cell polarity and tight junction formation.
  • To investigate the interaction between PATJ and histone deacetylase 7 (HDAC7).

Main Methods:

  • Generation of PATJ-deficient epithelial cells.
  • Three-dimensional (3D) cyst assays to assess polarity and lumen formation.
  • Co-immunoprecipitation to study protein interactions.
  • Gene expression analysis.
  • Pharmacological inhibition and genetic downregulation of HDAC7.

Main Results:

  • PATJ deficiency leads to defects in tight junctions, apical-basal polarity, and lumen formation.
  • PATJ directly associates with and inhibits HDAC7.
  • Inhibition of HDAC7 rescues polarity and lumen formation defects in PATJ-deficient cells.
  • PATJ regulates HDAC7-dependent cilia formation independently of its interaction with Pals1.
  • HDAC7 inhibition rescues polarity and lumen phenotypes in both PATJ- and Pals1-deficient cells.

Conclusions:

  • PATJ functions as a negative regulator of HDAC7 to control epithelial cell polarity, tight junction assembly, and lumen formation.
  • PATJ's role in regulating HDAC7-dependent processes, including cilia formation, represents a novel function distinct from its canonical role in the Crumbs complex.
  • The PATJ-HDAC7 axis modulates the transcriptional profile of epithelial cells, highlighting a new mechanism for regulating epithelial structure and function.

Keywords:
Cell polarityCrumbs-complexHDAC7Tight junctions

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