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A direct interaction of JAM-C with the tight junction scaffold protein ZO-2

Annika Schulte1, Mariel F Schwietzer1, Frauke Brinkmann1

  • 1Institute-associated Research Group Cell Adhesion and Cell Polarity, Institute of Medical Biochemistry, ZMBE, University of Münster, Von- Esmarch-Str. 56, D-48149, Münster, Germany.

Scientific Reports
|June 10, 2026
PubMed

Insights

Junctional Adhesion Molecule (JAM)-C directly interacts with the ZO-2 protein via its PDZ and SH3 domains. This interaction is crucial for tight junction function in epithelial cells, impacting cell adhesion and signaling.

Area of Science:

  • Cell biology
  • Molecular biology
  • Epithelial biology

Background:

  • Tight junctions are critical for epithelial barrier function, cell signaling, and adhesion.
  • They are formed by integral membrane proteins linked to cytoskeletal networks.

Purpose of the Study:

  • To investigate the interaction between Junctional Adhesion Molecule (JAM)-C and the zonula adherens (ZO) protein ZO-2.
  • To elucidate the molecular mechanisms underlying this interaction and its role in tight junction biology.

Main Methods:

  • Cell-based recruitment assays were employed to study protein interactions in living cells.
  • Biochemical in vitro experiments were conducted to confirm direct binding.
  • Immunofluorescence microscopy was used to determine protein localization in polarized epithelial cells.

Main Results:

  • JAM-C and ZO-2 were found to interact directly in a PDZ domain-dependent manner.
  • The interaction specifically requires PDZ domain 3 and the SH3 domain of ZO-2, forming a functional supramodule.
  • JAM-C localizes to tight junctions in polarized epithelial cells, and JAM-A suppresses JAM-C mRNA expression.

Conclusions:

  • The direct interaction between JAM-C and ZO-2 is a key event in tight junction assembly and function.
  • These findings provide insights into mechanosensing and liquid-liquid phase separation at tight junctions.
  • The study highlights the complex regulatory mechanisms governing tight junction protein expression and localization.

Keywords:
JAM-AJAM-CPDZ domainTight junctionZO-2

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