Mechanism and Dynamics of Cadherin Adhesion

Abstract

Cadherins are essential cell adhesion molecules involved in tissue morphogenesis and the maintenance of tissue architecture in adults. The adhesion and selectivity functions of cadherins are located in their extracellular regions. Biophysical studies show that the adhesive activity is not confined to a single interface. Instead, multiple cadherin domains contribute to binding. By contrast, the specificity-determining site maps to the N-terminal domains, which adhere by the reciprocal binding of Trp2 residues from opposing proteins. Structural cooperativity can transmit the effects of subtle structural changes or ligand binding over large distances in the protein. Increasingly, studies show that differential cadherin-mediated adhesion, rather than exclusive homophilic binding between identical cadherins, direct cell segregation and the organization of tissue interfaces during morphogenesis. Force measurements quantified both kinetic and strength differences between different classical cadherins that may underlie cell sorting behavior. Despite the complex adhesion mechanisms and differences in binding properties, cadherin-mediated cell adhesion is also regulated by many other biochemical processes. Elucidating the mechanisms by which cadherins organize cell junctions and tissue architecture requires not only quantitative, mechanistic investigations of cadherin function but also investigations of the biochemical and cellular processes that can modulate those functions.

A mouse model for nonsyndromic deafness (DFNB12) links hearing loss to defects in tip links of mechanosensory hair cells

“…2B), and is required for Ca 2ϩ chelation (Fig. 2C) (37,38). Several mutations that cause DFNB12 resemble the salsa mutation and affect Ca 2ϩ -binding motifs (LDRE, DXND, DXD; Fig.…”

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

“…Considering the known biology of adherens junctions, we reasoned from our experimental evidences and hypothesized that TiO 2 -NM by virtue of its size may have migrated into the nano-range size of the adherens junction (determined minimally by the length of a homophilically interacted complex of cadherin of B22.5 nm. 15 It then directly binds to and disrupt the extracellular homophilic interaction of VE-cadherin, the key molecule that maintains endothelial cell-cell integrity.…”

Cadherin Diffusion in Supported Lipid Bilayers Exhibits Calcium-Dependent Dynamic Heterogeneity

“…1, the slope of the MSD versus time plot, which is associated with the ensemble-averaged diffusion coefficient, decreased systematically with decreasing Ca 2þ concentration. At a concentration of 2 mM, where cadherin ectodomains were presumably saturated by Ca 2þ ions and possessed a relatively rigid elongated structure (1,3,4,8,15,38), the diffusion coefficient was determined to be 3.173 5 0.003 mm 2 /s. To understand this value, we measured the diffusion coefficient of fluorescently labeled lipids in a pure lipid bilayer (DOPC/DOPE-LR) at the same Ca 2þ concentration, and determined an almost identical value (3.124 5 0.005 mm 2 /s).…”

“…Cadherins are a group of transmembrane proteins that play essential roles in cell adhesion (1)(2)(3). They rely on Ca 2þ ions to maintain their elongated structure and enable their adhesive functions (4)(5)(6)(7)(8).…”