The αE(CD103)β7 integrin interacts with oral and skin keratinocytes in an E-cadherin-independent manner*.

The integrin αE(CD103)β7 (αEβ7) is expressed by intraepithelial lymphocytes, dendritic cells and regulatory T cells. It plays an important role in the mucosal immune system by retaining lymphocytes within the epithelium and is involved in graft rejection, immunity against tumours and the generation of gut-homing effector cells. In gut and breast, the ligand for αEβ7 is E-cadherin but in human oral mucosa and skin, there is evidence that lymphocytes use an alternative, unknown, ligand.

Endothelin-1-stimulated InsP3-induced Ca2+ release is a nexus for hypertrophic signaling in cardiac myocytes.

Ca(2+) elevations are fundamental to cardiac physiology-stimulating contraction and regulating the gene transcription that underlies hypertrophy. How Ca(2+) specifically controls gene transcription on the background of the rhythmic Ca(2+) increases required for contraction is not fully understood. Here we identify a hypertrophy-signaling module in cardiac myocytes that explains how Ca(2+) discretely regulates myocyte hypertrophy and contraction.

Cadherin adhesion depends on a salt bridge at the N-terminus.

There is now considerable evidence that cell adhesion by cadherins requires a strand exchange process in which the second amino acid at the N-terminus of the cadherin molecule, Trp2, docks into a hydrophobic pocket in the domain fold of the opposing cadherin. Here we show that strand exchange depends on a salt bridge formed between the N-terminal amino group of one cadherin molecule and the acidic side chain of Glu89 of the other. Prevention of this bond in N-cadherin by introducing the mutation Glu89Ala or by extending the N-terminus with additional amino acids strongly inhibited strand exchange.

The mechanism of cell adhesion by classical cadherins: the role of domain 1.

The mechanism by which classical cadherins mediate cell adhesion and, in particular, the roles played by calcium and Trp2, the second amino acid in the N-terminal domain, have long been controversial. We have used antibodies to investigate the respective contributions of Trp2 and calcium to the stability of the N-terminal domain of N-cadherin. Using a peptide antibody to the betaB strand in domain 1, which detects a disordered structure, we show that both Trp2 and calcium play crucial parts in regulating stability of the domain.

Role of the alphaI domain in ligand binding by integrin alphaEbeta7.

The I domain of integrin alphaE was modeled on the crystal structure of that in CD11b and mutated to produce an open (high affinity) or closed (low affinity) conformation. K562 transfectants expressing mutant alphaE and wild-type beta7 were tested for adhesion to E-cadherin-Fc. Downward displacement of the C terminus of the alphaI domain with a disulfide bridge enhanced adhesion and Mn(2+) dependency.