Format

Send to

Choose Destination
See comment in PubMed Commons below
J Invest Dermatol. 2014 Apr;134(4):1033-43. doi: 10.1038/jid.2013.401. Epub 2013 Sep 20.

Plakophilin-1 protects keratinocytes from pemphigus vulgaris IgG by forming calcium-independent desmosomes.

Author information

1
1] Department of Cell Biology, Emory University, Atlanta, Georgia, USA [2] Graduate Program in Biochemistry, Cell, and Developmental Biology, Emory University, Atlanta, Georgia, USA.
2
1] Department of Cell Biology, Emory University, Atlanta, Georgia, USA [2] Department of Dermatology, Emory University, Atlanta, Georgia, USA [3] Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.

Abstract

Plakophilin-1 (PKP-1) is an armadillo family protein critical for desmosomal adhesion and epidermal integrity. In the autoimmune skin-blistering disease pemphigus vulgaris (PV), autoantibodies (IgG) target the desmosomal cadherin desmoglein 3 (Dsg3) and compromise keratinocyte cell-cell adhesion. Here, we report that enhanced expression of PKP-1 protects keratinocytes from PV IgG-induced loss of cell-cell adhesion. PKP-1 prevents loss of Dsg3 and other desmosomal proteins from cell-cell borders and prevents alterations in desmosome ultrastructure in keratinocytes treated with PV IgG. Using a series of Dsg3 chimeras and deletion constructs, we find that PKP-1 clusters Dsg3 with the desmosomal plaque protein desmoplakin in a manner dependent on the plakoglobin-binding domain of the Dsg3 tail. Furthermore, PKP-1 expression transforms desmosome adhesion from a calcium-dependent to a calcium-independent and hyperadhesive state. These results demonstrate that manipulating the expression of a single desmosomal plaque protein can block the pathogenic effects of PV IgG on keratinocyte adhesion.

PMID:
24056861
PMCID:
PMC3961504
DOI:
10.1038/jid.2013.401
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center