TY - JOUR
T1 - Carboxyl terminus of plakophilin-1 recruits it to plasma membrane, whereas amino terminus recruits desmoplakin and promotes desmosome assembly
AU - Sobolik-Delmaire, Tammy
AU - Katafiasz, Dawn
AU - Wahl, James K.
PY - 2006/6/23
Y1 - 2006/6/23
N2 - 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. Whenexogenous 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 plasmamembrane. In addition,weshowed that amino acids 1-34 in the amino terminus were necessary for subsequent recruitment of desmoplakin to the membrane and desmosome assembly.
AB - 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. Whenexogenous 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 plasmamembrane. In addition,weshowed that amino acids 1-34 in the amino terminus were necessary for subsequent recruitment of desmoplakin to the membrane and desmosome assembly.
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U2 - 10.1074/jbc.M600570200
DO - 10.1074/jbc.M600570200
M3 - Article
C2 - 16632867
AN - SCOPUS:33745219875
SN - 0021-9258
VL - 281
SP - 16962
EP - 16970
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 25
ER -