Central role of the plakoglobin-binding domain for desmoglein 3 incorporation into desmosomes.
The carboxy-termini of classical cadherins and desmocollins have been shown to play an important role in initiating desmosome assembly. In this study we wanted to determine whether the carboxy- terminal cytoplasmic domains of desmoglein 3 are important for targeting it to the desmosome. By generating stably transfected A431 cell lines with chimeric constructs encoding for the extracellular domain of E-cadherin and the transmembrane and intracellular region of human desmoglein 3, we could show that the cytoplasmic tail is sufficient to target the protein to the desmosome. By generating truncations of the carboxy-terminus we investigated the importance of the various intracellular subdomains. Whereas the construct encoding the intracellular cadherin-type segment domain still allowed its incorporation into the desmosome, further truncation, leaving only the intracellular anchor domain, did not. Deletion of the 87 amino acid long plakoglobin-binding site within the intracellular cadherin-type segment domain demonstrated that this region is essential for targeting desmoglein 3 to the desmosome. Absent the plakoglobin-binding site the chimeric molecule colocalizes with beta-catenin rather than desmoplakin. We conclude that binding of plakoglobin to desmoglein 3 is an important step in desmosome assembly and leads to the incorporation of desmoglein 3 into the desmosome.
Andl
C D
CD
Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Stanley
J R
JR
D022005:Adherens Junctions / Q000378:metabolism; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002678:Chimera; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D051187:Desmocollins; D051184:Desmoglein 3; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000378:metabolism*; D006801:Humans; D017434:Protein Structure, Tertiary / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D051185:gamma Catenin
D015820:Cadherins; D003598:Cytoskeletal Proteins; C071894:DSG3 protein, human; C495294:DSP protein, human; D051187:Desmocollins; D051184:Desmoglein 3; D051182:Desmogleins; D051180:Desmoplakins; D011993:Recombinant Fusion Proteins; D051185:gamma Catenin