Plakoglobin: Kinetics of synthesis, phosphorylation, stability, and interactions with desmoglein and E‐cadherin

Pasdar, Manijeh; Li, Zhi; Chlumecky, Vera

doi:10.1002/cm.970320403

Cited by 43 publications

(33 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3A) as described previously (Pasdar et al, 1995). Using this fractionation procedure, the TritonX-100-soluble fraction contains most of the adherens junction components and desmosomal proteins not yet assembled into desmosomes, whereas the Triton-insoluble fraction mainly harbors fully assembled desmosomes (Pasdar et al, 1995). Interestingly, there was no substantial alteration in the steady-state level and distribution of plakoglobin and the major adherens junction and desmosomal proteins in case of β-catenin deletion.…”

Section: Resultsmentioning

confidence: 95%

“…Cellular lysates were fractionated in cytoplasmic, membrane-bound TritonX-100-soluble and TritonX-100-insoluble proteins (Fig. 3A) as described previously (Pasdar et al, 1995). Using this fractionation procedure, the TritonX-100-soluble fraction contains most of the adherens junction components and desmosomal proteins not yet assembled into desmosomes, whereas the Triton-insoluble fraction mainly harbors fully assembled desmosomes (Pasdar et al, 1995).…”

Section: Resultsmentioning

confidence: 99%

“…Cytoplasmic extracts were removed and cells were scraped into membrane extraction buffer (0.5% TritonX-100, 10 mM PIPES pH 6.8, 300 mM sucrose, 50 mM NaCl, 3 mM MgCl2, 10 mM Na4P2O7, 20 mM NaF, 1 mM Na3Vo4, 0.1mg/ml RNaseA, 0.1 mg/ml DNase 1, 1 mM PMSF and protease inhibitor cocktail) according to Pasdar et al (Pasdar et al, 1995) with some modifications (Caldelari et al, 2001). The TritonX-100-insoluble fraction was pelleted (20 minutes, 20,000 g) and dissolved by sonication and boiling in SDS-PAGE buffer.…”

Section: Rt-pcrmentioning

confidence: 99%

See 2 more Smart Citations

β-Catenin is not required for proliferation and differentiation of epidermal mouse keratinocytes

Posthaus

Williamson

Baumann

et al. 2002

Journal of Cell Science

View full text Add to dashboard Cite

Despite the pivotal role of β-catenin in a variety of biological processes, conditional β-catenin gene ablation in the skin of transgenic mice failed to affect interfollicular epidermal morphogenesis. We elucidated the molecular mechanisms underlying this phenomenon. Long-term cultures of homozygous, heterozygous and β-catenin-null mutant keratinocytes were established to demonstrate that epidermal keratinocyte proliferation, cell cycle progression and cyclin D1 expression occur independently of β-catenin and correlate with repression of transcription from Tcf/Lef-responsive promoters. Moreover, during differentiation,β-catenin-null cells assemble normal intercellular adhesion junctions owing to the substitution of β-catenin with plakoglobin, whereas the expression of the other adhesion components remains unaffected. Taken together, our results demonstrate that epidermal proliferation and adhesion are independent of β-catenin.

show abstract

Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Rt-pcrmentioning

confidence: 99%

See 1 more Smart Citation

β-Catenin is not required for proliferation and differentiation of epidermal mouse keratinocytes

Posthaus

Williamson

Baumann

et al. 2002

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…To visualize the entire cellular pool of proteins, cells were first fixed using formaldehyde and subsequently permeabilized using CSK extraction buffer. Alternatively, CSK extraction buffer was used first to permeabilize and extract the soluble pool of cellular proteins, followed by fixation with formaldehyde, allowing for the visualization of the cytoskeletonassociated pool of proteins (Pasdar and Nelson, 1988b;Pasdar et al, 1995), including those stabilized by association with the adhesive complexes.…”

Section: Nm23 Colocalizes At the Membrane With Plakoglobin And N-cadhmentioning

confidence: 99%

Plakoglobin interacts with and increases the protein levels of metastasis suppressor Nm23-H2 and regulates the expression of Nm23-H1

et al. 2010

View full text Add to dashboard Cite

Plakoglobin (c-catenin) is a homolog of b-catenin with similar dual adhesive and signaling functions. The adhesive function of these proteins is mediated by their interactions with cadherins, whereas their signaling activity is regulated by association with various intracellular partners. In this respect, b-catenin has a well-defined oncogenic activity through its role in the Wnt signaling pathway, whereas plakoglobin acts as a tumor/metastasis suppressor through mechanisms that remain unclear. We previously expressed plakoglobin in SCC9 squamous carcinoma cells (SCC9-P) and observed a mesenchymalto-epidermoid transition. Comparison of the protein and RNA profiles of parental SCC9 cells and SCC9-P transfectants identified various differentially expressed proteins and transcripts, including the nonmetastatic protein 23 (Nm23). In this study, we show that Nm23-H1 mRNA and Nm23-H2 protein are increased after plakoglobin expression. Coimmunoprecipitation and confocal microscopy studies using SCC9-P and various epithelial cell lines with endogenous plakoglobin expression revealed that Nm23 interacts with plakoglobin, cadherins and a-catenin. Furthermore, Nm23-H2 is the primary isoform involved in these interactions, which occur prominently in the cytoskeleton-associated pool of cellular proteins. In addition, we show that plakoglobinNm23 interaction requires the N-terminal (a-catenin interacting) domain of plakoglobin. Our data suggest that by increasing the expression and stability of Nm23, plakoglobin has a role in regulating the metastasis suppressor activity of Nm23, which may further provide a potential mechanism for the tumor/metastasis suppressor function of plakoglobin itself.

show abstract

“…PG is bound to desmogleins and desmocollins very soon after their synthesis and is known to traffic with the cadherins. 34 During the formation of intercellular junctions, PG plays a major role in the assembly of desmosomes. PG-null keratinocytes showed delayed incorporation of desmosomal components, including cadherins, into intercellular junctions, whereas adherens junctions were unaffected.…”

mentioning

confidence: 99%

Plakoglobin Rescues Adhesive Defects Induced by Ectodomain Truncation of the Desmosomal Cadherin Desmoglein 1

Simpson

Kojima

Cooper-Whitehair

et al. 2010

The American Journal of Pathology

View full text Add to dashboard Cite

Desmoglein 1 (Dsg1) is a desmosomal cadherin that is essential to epidermal integrity. In the blistering diseases bullous impetigo and staphylococcal scaldedskin syndrome, pathogenesis depends on cleavage of Dsg1 by a bacterial protease, exfoliative toxin A, which removes residues 1 to 381 of the Dsg1 ectodomain. However, the cellular responses to Dsg1 cleavage that precipitate keratinocyte separation to induce blister formation are unknown. Here, we show that ectodomain-deleted Dsg1 (⌬381-Dsg1) mimics the toxin-cleaved cadherin, disrupts desmosomes, and reduces the mechanical integrity of keratinocyte sheets. In addition, we demonstrate that truncated Dsg1 remains associated with its catenin partner , plakoglobin , and causes a reduction in the levels of endogenous desmosomal cadherins in a dose-dependent manner , leading us to hypothesize that plakoglobin sequestration by truncated Dsg1 destabilizes other cadherins. Accordingly, a triple-point mutant of the ectodomain-deleted cadherin, which is uncoupled from plakoglobin, does not impair adhesion, indicating that this interaction is essential to the pathogenic potential of truncated Dsg1. Moreover, we demonstrate that increasing plakoglobin levels rescues cadherin expression, desmosome organization, and functional adhesion in cells expressing ⌬381-Dsg1 or treated with exfoliative toxin A. Finally, we report that histone deacetylase inhibition up-regulates desmosomal cadherins and prevents the loss of adhesion induced by Dsg1 truncation. These findings further our understanding of the mechanism of exfoliative toxin-induced pathology and suggest novel strategies to suppress blistering in bulbous impetigo and staphylococcal scalded-skin syndrome. Desmosomes are specialized intercellular adhesive organelles crucial for maintaining the integrity of tissues that endure mechanical stress, especially the epidermis. 1The adhesive interface of desmosomes is built from specialized cadherin family members, including four desmogleins (Dsg1-4) and three desmocollins (Dsc1-3), assembled at junctions between epidermal keratinocytes. Desmogleins and desmocollins cooperate to mediate adhesion with cadherins on neighboring cells via ectodo-

show abstract

Plakoglobin: Kinetics of synthesis, phosphorylation, stability, and interactions with desmoglein and E‐cadherin

Cited by 43 publications

References 60 publications

β-Catenin is not required for proliferation and differentiation of epidermal mouse keratinocytes

β-Catenin is not required for proliferation and differentiation of epidermal mouse keratinocytes

Plakoglobin interacts with and increases the protein levels of metastasis suppressor Nm23-H2 and regulates the expression of Nm23-H1

Plakoglobin Rescues Adhesive Defects Induced by Ectodomain Truncation of the Desmosomal Cadherin Desmoglein 1

Contact Info

Product

Resources

About