Prototypical Type I E-cadherin and Type II Cadherin-7 Mediate Very Distinct Adhesiveness through Their Extracellular Domains

Abstract

Using a dual pipette assay that measures the force required to separate adherent cell doublets, we have quantitatively compared intercellular adhesiveness mediated by Type I (E-or N-cadherin) or Type II (cadherin-7 or -11) cadherins. At similar cadherin expression levels, cells expressing Type I cadherins adhered much more rapidly and strongly than cells expressing Type II cadherins. Using chimeric cadherins, we found that the extracellular domain exerts by far the dominant effect on cell adhesivity, that of E-cadherin conferring high adhesivity, and that of cadherin-7 conferring low adhesivity. Type I cadherins were incorporated to a greater extent into detergent-insoluble cytoskeletal complexes, and their cytoplasmic tails were much more effective in disrupting strong adherent junctions, suggesting that Type II cadherins form less stable complexes with ␤-catenin. The present study demonstrates compellingly, for the first time, that cadherins are dramatically different in their ability to promote intercellular adhesiveness, a finding that has profound implications for the regulation of tissue morphogenesis.Adhesive interactions, so essential to multicellular life, are mediated by a diversity of cell surface receptors. Prominent among them are the cadherins, calcium-dependent adhesion molecules central to tissue development and morphogenesis (1-3). The growing superfamily of cadherins is subdivided into five families: classical Type I cadherins, atypical Type II cadherins, desmosomal cadherins, protocadherins, and seven-pass transmembrane cadherins (4, 5). Classical Type I and desmosomal cadherins are found primarily in tissues where a high degree of cell cohesion is required for tissue integrity. Other types of cadherins are expressed in situations where cells are more motile, and intercellular interactions are more transitory (6 -9). It is increasingly clear that cadherins contribute to other cellular functions, including cell signaling, proliferation, differentiation, segregation, and migration (10 -17).Predictably, the pattern of cadherin expression during development is complex. For example, development of the neural crest involves epithelial to mesenchymal transitions, cell migration, cell aggregation, and cell differentiation (18), each of which is associated with tightly regulated, differential expression of Type I and II cadherins. Premigratory cells of the avian neural crest express first N-cadherin, and then they down-regulate N-cadherin and express Type II cadherin-6B, but later down-regulate it and induce expression of the Type II cadherin-7 as they migrate throughout the embryo (19,20). Another Type II cadherin, cadherin-11, is similarly induced in migrating neural crest cells of rat and Xenopus embryos (21-23). Cell grafting experiments in vivo verify that expression of cadherin-7 correlates with cell dispersion and migration along migratory pathways, whereas that of N-cadherin fosters strong intercellular cohesivity and failure to migrate (6).Regulation of cellular adhesion can be achieved in a v...

Cadherin-8 Is Required for the First Relay Synapses to Receive Functional Inputs from Primary Sensory Afferents for Cold Sensation

“…It was shown that different classic cadherins confer different adhesive strengths at cell junctions (Chu et al, 2006). Although the status of cad8 from this aspect is unknown, such differences imply that classic cadherin subtypes are functionally not identical.…”

Timing and kinetics of E‐ to N‐cadherin switch during neurulation in the avian embryo

“…Epithelial cells typically express E-cadherin whereas mesenchymal cells express various other cadherins such as N-cadherin, R-cadherin, cadherin-7, or cadherin-11. Consistent with this, biophysical studies demonstrated that E-cadherin mediates stronger bonds at the molecular level than any other cadherins (Dufour et al, 1999;Chu et al, 2006;Panorchan et al, 2006). Moreover, although E-cadherin and N-cadherin may transiently coexist in certain cells, they are generally mutually exclusive, and studies on epithelial cell lines or in mouse and Xenopus embryos in which E-and N-cadherins have been interchanged clearly indicate that they can only partially substitute each other (Luo et al, 2001;Kan et al, 2007;Wheelock et al, 2008;Nandadasa et al, 2009;Libusova et al, 2010).…”

Calpain-Mediated N-Cadherin Proteolytic Processing in Brain Injury

“…The adhesive function of cadherins depends on a stable connection with the actin cytoskeleton via ␤-catenin (Chu et al, 2006;Siu et al, 2007). The cytoplasmic tail in the juxtamembrane region of the cadherin is known as a functionally active adaptor supporting cadherin clustering and adhesive strength (Yap et al, 1998).…”