Endothelial Cell-to-Cell Junctions: Molecular Organization and Role in Vascular Homeostasis

Abstract

Intercellular junctions mediate adhesion and communication between adjoining endothelial and epithelial cells. In the endothelium, junctional complexes comprise tight junctions, adherens junctions, and gap junctions. The expression and organization of these complexes depend on the type of vessels and the permeability requirements of perfused organs. Gap junctions are communication structures, which allow the passage of small molecular weight solutes between neighboring cells. Tight junctions serve the major functional purpose of providing a "barrier" and a "fence" within the membrane, by regulating paracellular permeability and maintaining cell polarity. Adherens junctions play an important role in contact inhibition of endothelial cell growth, paracellular permeability to circulating leukocytes and solutes. In addition, they are required for a correct organization of new vessels in angiogenesis. Extensive research in the past decade has identified several molecular components of the tight and adherens junctions, including integral membrane and intracellular proteins. These proteins interact both among themselves and with other molecules. Here, we review the individual molecules of junctions and their complex network of interactions. We also emphasize how the molecular architectures and interactions may represent a mechanistic basis for the function and regulation of junctions, focusing on junction assembly and permeability regulation. Finally, we analyze in vivo studies and highlight information that specifically relates to the role of junctions in vascular endothelial cells.

Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain

“…While the claudins are critical for cell-cell adhesion, their function is dependent on the interaction with other TJ proteins (Bazzoni and Dejana, 2004;Hawkins and Davis, 2005;Huber et al, 2002a;Wolka et al, 2003). A disruption of TJ protein interactions may be responsible for the BBB integrity loss observed in this study, as opposed to changes in only a single protein.…”

“…Claudin-5 belongs to a family of proteins with over 20 members, characterized by 4 membrane-spanning domains, two extracellular loops and two cytoplasmic termini (Bazzoni and Dejana, 2004;Furuse, 1998, 2000). In the current study, disruption of paracellular permeability to [ 14 C] sucrose correlated with both a decrease and a 6-fold increase in claudin-5 expression at 24 and 72 h post-CFA, respectively.…”

Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node

“…These structures are formed by transmembrane proteins that are linked to the cytoskeleton by intracellular linker molecules. Adherens junctions mediate the adhesion of neighboring endothelial cells and regulate vascular permeability [8]. The major transmembrane protein of endothelial adherens junctions is vascular endothelial (VE)-cadherin [9].…”

“…It also regulates leukocyte trafficking and is involved in vascular permeability [15]. Most of these tight junction proteins are linked to the actin cytoskeleton via scaffolding proteins such as ZO-1 and ZO-2, both belonging to the MAGUK (membrane-associated guanylate kinase homologues) family [8,16,17]. Outside of structurally organized junctional complexes, the transmembrane protein platelet/endothelial cell adhesion molecule (PECAM)-1 is concentrated at the endothelial cell contacts.…”

Angiogenesis: The VE-Cadherin Switch

“…The organization of the endothelial intercellular contacts and the molecular description of the different junctional complexes are described in excellent reviews ( , Aurrand-Lions et al 2002 , ) and will not be reported here. Vestweber 2002 Bazzoni andDejana 2004 …”