ROLES OF PLAKOGLOBIN END DOMAINS IN DESMOSOME ASSEMBLY

Plakoglobin, a member of the armadillo family of proteins, is a compon ent of intercellular adhesive junctions. The central domain of plakogl obin comprises a highly conserved series of armadillo repeats that fac ilitate its association with either desmosomal or classic cadherins, o r with cytosolic proteins such as the tumor suppressor gene product ad enomatous polyposis coli, Sequences in the Nand C-terminal domains of plakoglobin are less highly conserved, and their possible roles in reg ulating plakoglobin's subcellular distribution and junction assembly a re still unclear, Here we have examined the role of plakoglobin end do mains 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. I n cell lines that express an N-terminal truncation of plakoglobin, an increase in the cytosolic pool of endogenous and ectopic plakoglobin w as observed that may reflect an increase in the stability of the prote in, Deletion of the N terminus did not have a dramatic effect on the s tructure of desmosomes in these cells, On the other hand, striking alt erations in desmosome morphology were observed in cells expressing C-t erminal truncations of plakoglobin. In these cell lines, ectopic plako globin incorporated into desmosomes, and extremely long junctions or g roups of tandemly linked desmosomes which remained well attached to ke ratin intermediate filaments, were observed, Together, these results s uggest that plakoglobin end domains play a role in regulating its subc ellular distribution, and that the presence of the C terminus limits t he size of desmosomes, perhaps through regulating protein-protein inte ractions required for assembly of the desmosomal plaque.