title: Plakophilin 2 couples actomyosin remodeling to desmosomal plaque assembly via RhoA.
abstract: Plakophilin 2 (PKP2), an armadillo family member closely related to p120 catenin (p120ctn), is a constituent of the intercellular adhesive junction, the desmosome. We previously showed that PKP2 loss prevents the incorporation of desmosome precursors enriched in the plaque protein desmoplakin (DP) into newly forming desmosomes, in part by disrupting PKC-dependent regulation of DP assembly competence. On the basis of the observation that DP incorporation into junctions is cytochalasin D-sensitive, here we ask whether PKP2 may also contribute to actin-dependent regulation of desmosome assembly. We demonstrate that PKP2 knockdown impairs cortical actin remodeling after cadherin ligation, without affecting p120ctn expression or localization. Our data suggest that these defects result from the failure of activated RhoA to localize at intercellular interfaces after cell-cell contact and an elevation of cellular RhoA, stress fibers, and other indicators of contractile signaling in squamous cell lines and atrial cardiomyocytes. Consistent with these observations, RhoA activation accelerated DP redistribution to desmosomes during the first hour of junction assembly, whereas sustained RhoA activity compromised desmosome plaque maturation. Together with our previous findings, these data suggest that PKP2 may functionally link RhoA- and PKC-dependent pathways to drive actin reorganization and regulate DP-IF interactions required for normal desmosome assembly.
authors.affiliation: Northwestern University Feinberg School of Medicine, Department of Pathology, Chicago, IL 60611, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Godsel
authors.forename: Adi D
authors.initials: AD
authors.lastname: Dubash
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Bass-Zubek
authors.forename: Evangeline V
authors.initials: EV
authors.lastname: Amargo
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Klessner
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Hobbs
authors.forename: Xinyu
authors.initials: X
authors.lastname: Chen
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Green
mesh_terms: D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D051177:Catenins / Q000378:metabolism; D002450:Cell Communication; D002460:Cell Line; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D008856:Microscopy, Fluorescence; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D051191:Plakophilins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: D000199:Actins; D015820:Cadherins; D051177:Catenins; D018994:Myosin Light Chains; D051191:Plakophilins; D049452:Green Fluorescent Proteins; D000205:Actomyosin; D011493:Protein Kinase C; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin; C000722347:CTNND1 protein, human