Roles of plakoglobin end domains in desmosome assembly.
Plakoglobin, a member of the armadillo family of proteins, is a component of intercellular adhesive junctions. The central domain of plakoglobin comprises a highly conserved series of armadillo repeats that facilitate its association with either desmosomal or classic cadherins, or with cytosolic proteins such as the tumor suppressor gene product adenomatous polyposis coli. Sequences in the N- and C-terminal domains of plakoglobin are less highly conserved, and their possible roles in regulating plakoglobin's subcellular distribution and junction assembly are still unclear. Here we have examined the role of plakoglobin end domains by stably expressing constructs lacking the N and/or C terminus of plakoglobin in A-431 cells. Our results demonstrate that myc-tagged plakoglobin lacking either end domain is still able to associate with the desmosomal cadherin desmoglein and incorporate into desmosomes. In cell lines that express an N-terminal truncation of plakoglobin, an increase in the cytosolic pool of en-dogenous and ectopic plakoglobin was observed that may reflect an increase in the stability of the protein. Deletion of the N terminus did not have a dramatic effect on the structure of desmosomes in these cells. On the other hand, striking alterations in desmosome morphology were observed in cells expressing C-terminal truncations of plakoglobin. In these cell lines, ectopic plakoglobin incorporated into desmosomes, and extremely long junctions or groups of tandemly linked desmosomes which remained well attached to keratin intermediate filaments, were observed. Together, these results suggest that plakoglobin end domains play a role in regulating its subcellular distribution, and that the presence of the C terminus limits the size of desmosomes, perhaps through regulating protein-protein interactions required for assembly of the desmosomal plaque.
Palka
H L
HL
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611, USA.
Green
K J
KJ
D000595:Amino Acid Sequence; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D016297:Mutagenesis, Site-Directed; D017830:Octoxynol; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D012995:Solubility; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051185:gamma Catenin
D003598:Cytoskeletal Proteins; D051182:Desmogleins; D051180:Desmoplakins; D051185:gamma Catenin; D017830:Octoxynol