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The role of junctional adhesion molecules in leukocyte transendothelial migration

Applicant Imhof Beat A.
Number 100697
Funding scheme Project funding
Research institution Département de Pathologie et Immunologie Faculté de Médecine / CMU Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Immunology, Immunopathology
Start/End 01.04.2003 - 31.03.2008
Approved amount 783'963.00
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Keywords (4)

Leukocytes; Lymphocytes; Platelets; Endothelium

Lay Summary (English)

Lead
Lay summary
The junctional adhesion molecules (JAMs) have been recently described as interendothelial junctional molecules and as integrin ligands. Jam-C-/- mice exhibit multilobular pneumonia concomitant with poor survival of the mice under conventional housing conditions. The number of circulating granulocytes in these mice is increased as compared to control animals. This phenotype probably reflects the different functions of JAM-C expressed by endothelial and mesenchymal cells. Indeed the deregulation in the number of circulating granulocytes is caused by the lack of JAM-C expression on endothelial cells since rescuing endothelial expression of the protein in the Jam-C-/- mice is sufficient to restore homeostasis. More importantly, the rescue of vascular JAM-C expression is accompanied by better survival of deficient mice, suggesting that endothelial expression of JAM-C is mandatory for animal survival from opportunistic infections and fatal pneumonia.Tight junctions are crucial for the establishment and maintenance of cell polarity, transendothelial migration of leukocytes and angiogenic remodelling of the endothelial tissue. Using a carcinoma cell line we tested whether JAM-C could affect tight junctions and migratory properties of these cells. We found that transfection of JAM-C improves the tight junctional barrier in cells devoid of JAM-C expression. This is dependent on serine 281 in the cytoplasmic tail of JAM-C because serine mutation into alanine abolishes the specific localization of JAM-C in tight junctions and establishment of cell polarity. More importantly, the same mutation stimulates integrin-mediated cell migration and adhesion via the modulation of ?1 and ?3 integrin activation.These results suggest that JAM-C is an extremely versatile molecule involved in migratory functions of cells of the immune system and in angiogenesis.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
120184 Junctional adhesion molecules, versatile players in inflammatory immune reactions 01.04.2008 Project funding

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