The complexus adhaerens of mammalian lymphatic endothelia revisited: a junction even more complex than hitherto thought

Abstract

The significance of a special kind of VE-cadherin-based, desmoplakin- and plakoglobin-containing adhering junction, originally identified in certain endothelial cells of the mammalian lymphatic system (notably the retothelial cells of the lymph node sinus and a subtype of lining endothelial cells of peripheral lymphatic vessels), has been widely confirmed and its importance in the formation of blood and lymph vessels has been demonstrated in vivo and in vitro. We have recently extended the molecular and structural characterization of the complexus adhaerens and can now report that it represents a rare and special combination of components known from three other major types of cell junction. It comprises zonula adhaerens proteins (VE-cadherin, alpha- and beta-catenin, protein p120(ctn), and afadin), desmosomal plaque components (desmoplakin and plakoglobin), and tight-junction proteins (claudin-5 and ZO-1) and forms junctions that vary markedly in size and shape. The special character and the possible biological roles of the complexus adhaerens and its unique ensemble of molecules in angiogenesis, immunology, and oncology are discussed. The surprising finding of claudin-5 and protein ZO-1 in substructures of retothelial cell-cell bridges, i.e. structures that do not separate different tissues or cell layer compartments, suggests that such tight-junction molecules are involved in functions other than the "fence" and "barrier" roles of zonulae occludentes.

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

“…Localization of claudin-5, JAM-A, JAM-C, ESAM-1 and ZO-1 characterizes the molecular composition of tight junctions between the sinus-lining endothelial cells of the subcapsular and medullary sinuses and provides the molecular basis for the diffusion barrier established at this level. Our findings are in agreement with a previous study, which reported the presence of unique cell contacts between sinus-lining endothelium, designated complexus adhaerens in human lymph nodes [30]. The name complexus adhaerens was coined to describe this specific cell-tocell-contact, combining molecular elements from adherens junctions such as VE-cadherin, a-and b-catenin, with prominent desmosomal plaque proteins such a desmoplakin and plakoglobin and several tight junction proteins such as claudin-5, JAM-A and ZO-1.…”

Processus and recessus adhaerentes: giant adherens cell junction systems connect and attract human mesenchymal stem cells

“…Clearly, our finding of ezrin as a major cytoskeletal component in MSC processes should now lead to investigations regarding its presence and fuction in the formation of processes of mesenchymal cells during early embryogenesis or in adhering junction-stabilized cytoplasmic projections of retothelial cells of the sinus of lymph nodes (cf. Hämmerling et al 2006).…”

Structure and function of rat lymph nodes

“…The sinus lining cells are linked by junctions termed "complexus adhaerentes" (Schmelz et al, 1994). Recently, Hämmerling et al (2006) showed that the complexus adhaerentes of mammalian lymphatic endothelia comprises zonula adherens proteins (VEcadherin, -and -catenin, protein p120 ctn , and afadin), desmosomal plaque components (desmoplakin and plakoglobin) and tight-junction proteins (claudin-5 and ZO-1).…”