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Desmosomal and Classical Cadherins in the Molecular Organization of Adhesive Cell-cell Junctions

Suzanne Marie Norvell

出版	Northwestern University, 1999
URL	http://books.google.com.hk/books?id=NCAdAQAAMAAJ&hl=&source=gbs_api

註釋

Two prominent cell-cell junctions in epithelial cells are adherens junctions and desmosomes. Both adherens junctions and desmosomes contain calcium dependent transmembrane adhesion molecules termed cadherins. Adherens junctions comprise classical cadherins such as E-cadherin, and desmosomes contain desmosomal cadherins termed desmogleins and desmocollins. There are three isoforms of both desmogleins and desmocollins that are expressed in a cell type and differentiation specific manner. The relative contributions of the different desmosomal cadherins to desmosome assembly are unclear. To examine the assembly properties of distinct cadherins, we established A431 cell lines stably expressing different full length desmosomal cadherin isoforms as well as chimeric molecules of desmoglein and E-cadherin. Desmoglein 1 (Dsg1), which is not normally expressed in A431 epithelial cells, localized diffusely at the cell surface and even moderate levels disrupted desmosomes and resulted in decreased endogenous Dsc2 levels in A431 cells. Likewise, a chimera comprising the Dsg1 intracellular domain and the extracellular domain of E-cadherin (Ecad.Dsg1), also disrupted desmosomes. Ecad.Dsg1, however, localized in distinct patches at cell-cell interfaces, perhaps due to E-cadherin extracellular domain interactions. In addition, Ecad.Dsg1 formed a complex with beta-catenin. Taken together, these results demonstrate that the Dsg1 tail disrupts desmosomes in A431 cells, and also provide evidence for lateral complexes of the E-cadherin extracellular domain and novel interactions of the Dsg1 cytoplasmic domain. Ectopic expression of Desmoglein 2 (Dsg2) or Desmocollin 2 (Dsc2), which are endogenously expressed in A431 cells, did not affect desmosome assembly and Dsg2 and Dsc2 localized in a punctate, desmosomal pattern at cell-cell interfaces, even when overexpressed. To address whether Dsg1 specific desmosome disruption was potentially due to plakoglobin (Pg) sequestration by the Dsg1 tail, plakoglobin was stably introduced into Dsg1 expressing cells. Cells stably expressing Dsg1 and Pg exhibited normal desmosome morphology but levels of endogenous Dsc2 remained low, suggesting that Pg plays a critical role in Dsg1 mediated disruption, but that it may not be the sole contributing factor. In summary, these data demonstrate that A431 cells have a high tolerance for varying levels of endogenous desmosomal cadherins while moderate levels of a foreign desmosomal cadherin results in desmosome disruption.