Structure and Function of Cadherin Extracellular Regions

Abstract

Cell-surface glycoproteins of the cadherin superfamily are defined by the presence of extracellular cadherin (EC) β-sandwich domains in their extracellular regions. EC domains adopt a fold similar to immunoglobulin domains, but most EC domains ligate calcium through stereotyped sites positioned between successive domains; Ca 2+ -binding at these sites rigidifies cadherin extracellular regions. Although the superfamily is highly diverse and may serve numerous functions, the best-characterized members are the vertebrate "classical" cadherins, which mediate cell-cell adhesion via homodimerization between their membrane-distal EC1 domains. Nonclassical and invertebrate cadherins have evolved distinct mechanisms for cell recognition and adhesion, and are only now beginning to be understood.

Single-Cell RNA Sequencing Atlas From a Bivalve Larva Enhances Classical Cell Lineage Studies

“…Moreover, this cluster expresses orthologs of epidermal cells from the acoel Isodiametra pulchra and the annelid Capitella teleta that are associated with extracellular matrix factors and tight junctions such as annexin, cadherins, and claudin family members (Supplementary Figure 4 and Supplementary Tables 1-3; Duruz et al, 2020;Sur and Meyer, 2021). Claudin is a transmembrane protein that is a crucial component of tight junctions in cells and cadherins are a type of cell adhesion molecules important for epithelium formation (Broders and Thiery, 1995;Krause et al, 2008;Piontek et al, 2008;Shapiro, 2016). For annexin, while playing a role in calcium-dependent membrane-binding and constituting an ectodermal marker in several metazoans (Meyer and Seaver, 2009;Duruz et al, 2020;Sur and Meyer, 2021), our results find this gene expressed also in ciliary and shell field cells (Supplementary Figure 4 and Supplementary Tables 1-3).…”

Regulation of multiple dimeric states of E-cadherin by adhesion activating antibodies revealed through Cryo-EM and X-ray crystallography

“…The stable final form of the trans interaction is thought to be mediated by the "strandswap" dimer, named because it is mediated by the N-terminal beta strand in EC1 participating in a domain swap with the similar strand in the opposing cadherin EC1 22,[30][31][32][33] . The Trp2 residue of that strand in the monomer leaves a hydrophobic pocket in its own EC1 to enter the hydrophobic pocket of the opposing EC1 to form the dimer.…”

“…This transition state brings the beta strands and Trp2 residues in proximity to each other, creating a favorable environment for the strand-swapping to take place. The Trp2 residues in the X-dimer are thought to flip to form a strand-swapped X-dimer 33 , and then this extends into the full strand-swap dimer [31][32][33] . Blocking the necessary salt bridge by mutating either K14 of D138 blocks the X intermediate, and these mutants are completely defective in cell adhesion.…”