Carboxyl terminus of Plakophilin-1 recruits it to plasma membrane, whereas amino terminus recruits desmoplakin and promotes desmosome assembly.

Sobolik-Delmaire T, Katafiasz D, Wahl JK
J Biol Chem. 2006 281 (25): 16962-16970

PMID: 16632867 · DOI:10.1074/jbc.M600570200

Plakophilins are armadillo repeat-containing proteins, initially identified as desmosomal plaque proteins that have subsequently been shown to also localize to the nucleus. Loss of plakophilin-1 is the underlying cause of ectodermal dysplasia/skin fragility syndrome, and skin from these patients exhibits desmosomes that are reduced in size and number. Thus, it has been suggested that plakophilin-1 plays an important role in desmosome stability and/or assembly. In this study, we used a cell culture system (A431DE cells) that expresses all of the proteins necessary to assemble a desmosome, except plakophilin-1. Using this cell line, we sought to determine the role of plakophilin-1 in de novo desmosome assembly. When exogenous plakophilin-1 was expressed in these cells, desmosomes were assembled, as assessed by electron microscopy and immunofluorescence localization of desmoplakin, into punctate structures. Deletion mutagenesis experiments revealed that amino acids 686-726 in the carboxyl terminus of plakophilin-1 are required for its localization to the plasma membrane. In addition, we showed that amino acids 1-34 in the amino terminus were necessary for subsequent recruitment of desmoplakin to the membrane and desmosome assembly.

MeSH Terms (14)

Amino Acid Sequence Calcium Cell Line Cell Line, Tumor Cell Membrane Cell Nucleus Desmoplakins Desmosomes Gene Deletion Humans Molecular Sequence Data Plakophilins Protein Structure, Tertiary Sequence Homology, Amino Acid

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