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Junctional adhesion molecule-a participates in the formation of apico-basal polarity through different domains

Daniela Rehder1, Sandra Iden, Ines Nasdala

  • 1Institute of Cell Biology, ZMBE, University of Münster, D-48149 Münster, Germany.

Experimental Cell Research
|August 22, 2006
PubMed

Insights

Junctional adhesion molecule (JAM)-A is crucial for epithelial cell polarity and cyst formation. Specific regions within JAM-A, beyond the C-terminal PDZ motif, are essential for its function in maintaining apico-basal polarity and tight junctions.

Area of Science:

  • Cell Biology
  • Epithelial Biology
  • Molecular Cell Biology

Background:

  • Junctional adhesion molecule (JAM)-A is an integral membrane protein found at epithelial tight junctions.
  • JAM-A interacts with the cell polarity protein PAR-3, suggesting a role in cell organization.

Purpose of the Study:

  • To investigate the role of JAM-A in the development of apico-basal polarity in epithelial cells.
  • To identify specific regions of JAM-A critical for its function in polarity and tight junction formation.

Main Methods:

  • Generated MDCK II cell lines expressing inducible JAM-A mutants.
  • Assessed cyst formation in 3D matrix and tight junction integrity.
  • Analyzed localization and function of JAM-A mutants lacking specific domains or motifs.

Main Results:

  • Downregulation of JAM-A impaired cyst formation, indicating its requirement for apico-basal polarity.
  • JAM-A mutants that mislocalized severely disrupted cyst development and tight junction formation.
  • Mutants lacking the C-terminal PDZ-binding motif still impaired polarity, suggesting other cytoplasmic tail regions are important.
  • A mutant lacking the first Ig-like domain, despite proper localization, interfered with polarity and tight junctions.

Conclusions:

  • JAM-A plays a critical role in establishing and maintaining apico-basal polarity in epithelial cells.
  • Regions within the JAM-A cytoplasmic tail, in addition to the PDZ-binding motif, are essential for its function.
  • The first Ig-like domain of JAM-A is also important for its role in cell polarity and tight junction formation.

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