Different roles of cadherins in the assembly and structural integrity of the desmosome complex
Adhesion between cells is established by the formation of specialized intercellular junctional complexes, such as desmosomes. Desmosomes comprise two members of the cadherin superfamily of cell adhesion proteins, desmocollin (Dsc) and desmoglein (Dsg), but their combinatorial roles in desmosome assembly is not understood. To uncouple desmosome assembly from other cell-cell adhesion complexes, we used micro-patterned substrates of Dsc2aFc and/or Dsg2Fc and collagen IV; we show that Dsc2aFc, but not Dsg2Fc, was necessary and sufficient to recruit desmosome-specific desmoplakin into desmosome puncta and produce strong adhesive binding. Single Molecule Force Spectroscopy showed that monomeric Dsc2a, but not Dsg2, formed Ca2+-dependent homophilic bonds, and that Dsg2 formed Ca2+-independent heterophilic bonds with Dsc2a. A W2A mutation in Dsc2a inhibited Ca2+-dependent homophilic binding, similar to classical cadherins, and Dsc2aW2A, but not Dsg2W2A, was excluded from desmosomes in MDCK cells. These results indicate that Dsc2a, not Dsg2, is required for desmosome assembly via homophilic Ca2+- and W2/strand swap-dependent binding, and that Dsg2 may be involved later in regulating a switch to Ca2+-independent adhesion in mature desmosomes.
- Research Organization:
- Ames Lab., Ames, IA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC)
- DOE Contract Number:
- DE-AC02-07CH11358
- OSTI ID:
- 1157616
- Report Number(s):
- IS0J 8333
- Journal Information:
- Journal of Cell Science, Vol. 127, Issue 10; ISSN 0021-9533
- Country of Publication:
- United States
- Language:
- English
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