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Expression of junctional adhesion molecule-A prevents spontaneous and random motility

Gianfranco Bazzoni1, Paolo Tonetti, Luca Manzi

  • 1Laboratory of Systems Biology, Department of Immunology and Cell Biology, Istituto di Ricerche Farmacologiche Mario Negri, 20157 Milano, Italy. bazzoni@marionegri.it

Journal of Cell Science
|January 20, 2005
PubMed

Insights

Junctional adhesion molecule-A (JAM-A) prevents cell motility by regulating cytoskeletal and adhesive structures. Its absence enhances cell movement, a process reversed by targeting glycogen synthase kinase-3beta (GSK-3beta).

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Junctional adhesion molecule-A (JAM-A) is a cell-surface glycoprotein found at intercellular junctions.
  • JAM-A interacts with intracellular proteins through specific binding residues.
  • The functional role of JAM-A in cell motility and its associated pathways remains to be fully elucidated.

Purpose of the Study:

  • To investigate the functional consequences of JAM-A expression on endothelial cell motility.
  • To determine the molecular mechanisms underlying JAM-A's regulation of cell movement.
  • To explore the relationship between JAM-A, protein kinase Czeta (PKCzeta), and glycogen synthase kinase-3beta (GSK-3beta) in cell motility.

Main Methods:

  • Generation of JAM-A-deficient endothelial cells from knockout mice.
  • Transfection of cells with full-length JAM-A or JAM-A deletion mutants.
  • Treatment of cells with glycogen synthase kinase-3beta (GSK-3beta) inhibitors.
  • Analysis of cell motility, actin protrusions, microtubule stability, and focal adhesion formation.

Main Results:

  • Absence of JAM-A significantly enhanced spontaneous and random endothelial cell motility.
  • Enhanced motility in JAM-A-negative cells was reversed by JAM-A re-expression or GSK-3beta inhibition.
  • JAM-A absence led to increased actin protrusions, reduced microtubule stability, and impaired focal adhesion formation.
  • The effects of JAM-A absence were dependent on its PSD95-Dlg-ZO1-binding residues.

Conclusions:

  • JAM-A expression acts as a negative regulator of endothelial cell motility.
  • JAM-A likely influences motility by modulating cytoskeletal dynamics and focal adhesion formation.
  • The regulatory role of JAM-A in cell motility is, at least in part, dependent on its interaction with intracellular proteins via PSD95-Dlg-ZO1-binding residues and potentially involves the GSK-3beta pathway.

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