Cadherin Adhesion: Mechanisms and Molecular Interactions

Abstract

Cadherins constitute a superfamily of cell-cell adhesion molecules expressed in many different cell types that are required for proper cellular function and maintenance of tissue architecture. Classical cadherins are the best understood class of cadherins. They are single membrane spanning proteins with a divergent extracellular domain of five repeats and a conserved cytoplasmic domain. Binding between cadherin extracellular domains is weak, but strong cell-cell adhesion develops during lateral clustering of cadherins by proteins that link the cadherin cytoplasmic domain to the actin cytoskeleton. Understanding how different regions of cadherins regulate cellcell adhesion has been a major focus of study. Here, we examine evidence of the structure and function of the extracellular domain of classical cadherins in regard to the control of recognition and adhesive contacts between cadherins on opposing cell surfaces. Early experiments that focused on understanding the homotypic, Ca ++ -dependent characteristics of cadherin adhesion are discussed, and data supporting the widely accepted cis-and trans-dimer models of cadherins are analyzed.

TGF-β1 affects cell-cell adhesion in the heart in an NCAM1-dependent mechanism

“…The classical adhesion receptor present in the adherens junctions and desmosomes is composed of cadherins. The extracellular domain of cadherins promotes homophilic interactions that mediate strong myocyte-myocyte adhesion and allow proper maintenance of tissue structure [5]. In addition to cadherins, other receptors are targeted to the intercalated discs and regulate cardiomyocytes’ coupling.…”

Discovering the Molecular Components of Intercellular Junctions--A Historical View

“…Luckily, effective cDNA cloning methods were already at hand so that in only a few years the major cell type-specific cadherins were sequenced and could be localized by effective antibodies: E-cadherin (Gallin et al 1983;Schuh et al 1986;Bussemakers et al 1993), N-cadherin (Hatta and Takeichi 1986;Hatta et al 1987Hatta et al , 1988Nose and Takeichi 1986), P-cadherin (Nose and Takeichi 1986;Nose et al 1987), and the vascular endothelium-characteristic VE-cadherin (Lampugnani et al 1995;Dejana 1996;Dejana et al 2000). Finally, more than 50 members of a large "superfamily" in mammals have been identified, including so-called "classic" cadherins, "type II cadherins," and "protocadherins" (reviews : Takeichi 1988: Takeichi , 1990Gumbiner 1996;Nollet et al 2000;Angst et al 2001;Wheelock and Johnson 2003;Perez and Nelson 2004;Halbleib and Nelson 2006), not to mention the bewildering numbers of cadherins and their splice variants in some other parts of the animal kingdom (for arthropod cadherins, see, e.g., Hsu et al 2009). Each of these newly discovered cadherins immediately produced "daughter avalanches" of publications dealing with the molecular interactions of the specific cadherins with each other and with AJ plaque proteins, the regulation of assembly or disassembly of AJs, and the functions of different cadherins during development and in the mature tissue, beginning with the study of Matsunaga et al (1988; see also Meng and Takeichi 2009).…”

Tools for studying the role of N-cadherin mediated extracellular interaction in neuronal development and function

“…1). 10 In the strand-swap binding model of classical cadherins, first visualized in high resolution crystal structures of N-cadherin EC1, the side chain of W2 intercalates into the hydrophobic pocket of the opposing cadherin, thereby "swapping" the N-terminal β-strands (A-strand) of paired EC1 domains. 12 Mutating the second tryptophan to alanine (W2A) or other conserved residues within the hydrophobic pocket inhibited N-cadherin mediated D o n o t d i s t r i b u t e .…”