Interendothelial junctions and their role in the control of angiogenesis, vascular permeability and leukocyte transmigration.
Endothelial cell-cell junctions play an important role in vascular hemostasis. The two junctional proteins VE-cadherin and JAM-1 are localized at adherens and tight junctions, respectively. VE-cadherin is only expressed by endothelial cells, suggesting that it can exert cell specific function. Absence of VE-cadherin or blocking of its adhesive activity prevents a normal organization of new vascular structures, suggesting that VE-cadherin may be a molecular target of antiangiogenic therapy. In addition, the ability of permeability-increasing agents and adherent leukocytes to modify VE-cadherin/catenin organization may be related to a role in the control of vascular permeability and leukocyte infiltration. JAM-1 is an integral membrane protein expressed in endothelial and epithelial cells. Its extracellular domain can dimerize and bind homophilically. The intracellular domain (and in particular a PDZ-binding motif) enables JAM-1 to interact with structural and signaling proteins. Study of the molecular interactions of JAM-1 may help explain mechanisms of JAM-mediated function, such as control of paracellular permeability and leukocyte transmigration.
Dejana
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Istituto di Ricerche Farmacologiche Mario Negri, Italy. dejana@marionegri.it
Spagnuolo
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Bazzoni
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G
D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D002199:Capillary Permeability; D015815:Cell Adhesion Molecules; D002634:Chemotaxis, Leukocyte; D004730:Endothelium, Vascular / Q000166:cytology* / Q000648:ultrastructure; D017629:Gap Junctions / Q000737:chemistry / Q000502:physiology*; D006487:Hemostasis; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D018919:Neovascularization, Physiologic; D011956:Receptors, Cell Surface
D015820:Cadherins; D015815:Cell Adhesion Molecules; C407243:F11R protein, human; D008565:Membrane Proteins; D011956:Receptors, Cell Surface