Extracellular domain of pemphigus vulgaris antigen (desmoglein 3)nediates weak homophilic adhesion

Masayuki Amagai, S. Kárpáti, Vera Klaus-Kovtun, Mark C. Udey, John R. Stanley

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Pemphigus vulgaris antigen is in the cadherin supergene family. We hypothesised that the extracellular domain of pemphigus vulgaris antigen might mediate homophilic cell adhesion because 1) the originally described cadherins (e.g., E-cadherin) mediate this type of adhesion, 2) pemphigus vulgaris antigen is localized in desmosomes that are cell adhesion Junctions, and 3) autoantibodies in pemphigus vulgaris patients cause loss of cell adhesion. To test this hypothesis we used a system developed for E-cadherin that, when transfected into L cells (mouse fibroblasis), has been shown to cause aggregation. Because this aggregation requires the cytoplasmic domain of E-cadherin to bind to catenins, we made a chimeric cDNA construct that encodes the extracellular domain of pemphigus vulgaris antigen and the cytoplasmic domain of E-cadherin. Analysis by immunofluorescence and flow cytometry with pemphigus vulgaris sera indicated that the pemphigus vulgaris antigen extracellular domain of this chimeric molecule (PVEC) was expressed on the cell surface of transiently transfected cells and permanently transfected L-cell clones. Immunoprecipitation of the chimeric molecule from extracts of these clones showed that the E-cadherin cytoplasmic domain bound catenins. Surprisingly, these L-cell clones displayed only slight aggregation compared to am Lcell clone transfected with E-cadherin. This weak aggregation was, however, specific and homophilic, as determined by cell sorting of only PVEC transfectants into aggregates from mixtures of PVEC and neomycin resistance gene transfectants, one of which was labeled with a fluorescent dye. We conclude that the extracellular domain of pemphigus vulgaris antigen mediates weak homophilic adhesion and is not interchangeable in function with the extracellular domain of E-cadherin.

Original languageEnglish
Pages (from-to)609-615
Number of pages7
JournalJournal of Investigative Dermatology
Volume103
Issue number4
Publication statusPublished - Oct 1994

Fingerprint

Desmoglein 3
Pemphigus
Cadherins
Adhesion
Antigens
Cell adhesion
Clone cells
Agglomeration
Clone Cells
Cell Adhesion
Catenins
Desmosomes
Molecules
Intercellular Junctions
Neomycin
Flow cytometry
Fluorescent Dyes
Sorting
Immunoprecipitation
Autoantibodies

Keywords

  • desmosome / cadherin / autoimmune / catenin

ASJC Scopus subject areas

  • Dermatology

Cite this

Extracellular domain of pemphigus vulgaris antigen (desmoglein 3)nediates weak homophilic adhesion. / Amagai, Masayuki; Kárpáti, S.; Klaus-Kovtun, Vera; Udey, Mark C.; Stanley, John R.

In: Journal of Investigative Dermatology, Vol. 103, No. 4, 10.1994, p. 609-615.

Research output: Contribution to journalArticle

Amagai, Masayuki ; Kárpáti, S. ; Klaus-Kovtun, Vera ; Udey, Mark C. ; Stanley, John R. / Extracellular domain of pemphigus vulgaris antigen (desmoglein 3)nediates weak homophilic adhesion. In: Journal of Investigative Dermatology. 1994 ; Vol. 103, No. 4. pp. 609-615.
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