A role for plakophilin-1 in the initiation of desmosome assembly
Article first published online: 29 JUN 2005
Copyright © 2005 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 96, Issue 2, pages 390–403, 1 October 2005
How to Cite
Wahl, J. K. (2005), A role for plakophilin-1 in the initiation of desmosome assembly. J. Cell. Biochem., 96: 390–403. doi: 10.1002/jcb.20514
- Issue published online: 21 SEP 2005
- Article first published online: 29 JUN 2005
- Manuscript Accepted: 31 MAR 2005
- Manuscript Received: 2 MAR 2005
- NIH (to JKW). Grant Number: P20 RR018759
- cell–cell adhesion
Plakophilins (pkp-1, -2, and -3) comprise a family of armadillo-repeat containing proteins that are found in the desmosomal plaque and in the nucleus. Plakophilin-1 is most highly expressed in the suprabasal layers of the epidermis and loss of plakophilin-1 expression results in skin fragility-ectodermal dysplasia syndrome, which is characterized by a reduction in the number and size of desmosomes in the epithelia of affected individuals. To investigate the role of plakophilin-1 during desmosome formation, we fused plakophilin-1 to the hormone-binding domain of the estrogen receptor to create a fusion protein (plakophilin-1/ER) that can be activated in cell culture by the addition of 4-hydroxytamoxifen. When plakophilin-1/ER was expressed in A431 cells it was incorporated into endogenous desmosomes and did not disrupt desmosome formation. A derivative of A431 cells (A431D) do not form desmosomes, even though they express all the components believed to be necessary for desmosome assembly. Expression and activation of plakophilin-1/ER in A431D cells resulted in punctate desmoplakin staining on the cell surface. Co-expression of a classical cadherin (N-cadherin) and plakophilin-1/ER in A431D cells resulted in punctate desmoplakin staining at cell–cell borders. These data suggest that plakophilin-1 can induce assembly of desmosomal components in A431D cells in the absence of a classical cadherin; however a classical cadherin (N-cadherin) is required to direct assembly of desmosomes between adjacent cells. The activatable plakophilin-1/ER system provides a unique culture system to study the assembly of the desmosomal plaque in culture. © 2005 Wiley-Liss, Inc.