Related Experiment Video
Updated: Jun 23, 2026

Simultaneous Study of the Recruitment of Monocyte Subpopulations Under Flow In Vitro
Published on: November 26, 2018
JAM-C induces endothelial cell permeability through its association and regulation of {beta}3 integrins
Xiaochun Li1, Milena Stankovic, Boris P-L Lee
1Centenary Institute of Cancer Medicine and Cell Biology, Locked bag#6, Newtown, NSW, Australia.
Objective:
The molecular mechanisms regulating vascular permeability are only now being elucidated. The junctional adhesion molecule (JAM) JAM-C has been linked to the induction of vascular permeability. We sought to understand the mechanism whereby JAM-C may disrupt junctional integrity in endothelial cells (ECs).
Methods And Results:
We show here that JAM-C alters permeability through modulation of integrin activity. JAM-C overexpression results in an increase in JAM-C at junctions and an increase in permeability. Conversely, knockdown of JAM-C by siRNA results in a reduction in permeability. JAM-C associates with alphavbeta3 integrin and regulates its localization and activity. JAM-C also inhibits the activation state of the beta(1) integrin although it does not associate with this integrin. These changes induced on the integrins are mediated through regulation of the small GTPase, Rap1b but not Rap1a. Thrombin, a powerful inductor of vascular leak, causes localization of JAM-C into the junctions, whereas angiopoietin-1, an inhibitor of permeability, prevents JAM-C translocation.
Conclusions:
The regulation of EC junctional integrity involves the coordinated and dynamic modification of localization and activity of junctional stabilizers such as the integrin beta(3) and the destabilizer, JAM-C.
Related Concept Videos
Intracellular Signaling Affects Focal Adhesions
Some...
Activation of Integrins
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Immunoglobulin-like Cell Adhesion Molecules
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Integrins
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Regulation of Angiogenesis and Blood Supply
Anchoring Junctions

