Plakophilin 2: a critical scaffold for PKCα that regulates intercellular junction assembly

Bass-Zubek, Amanda E.; Hobbs, Ryan P.; Amargo, Evangeline V.; García, Nahuel Aquiles; Hsieh, Sherry N.; Chen, Xinyu; Wahl, James K.; Denning, Mitchell F.; Green, Kathleen J.

doi:10.1083/jcb.200712133

Cited by 142 publications

(164 citation statements)

References 30 publications

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“…Careful examination of the cytoplasmic plakophilin and desmoplakin localization did not reveal extensive overlap suggesting these proteins were not present in biosynthetic complexes previously identified in A431 cells (Bass-Zubek et al, 2008). Because the plakophilin-2 544 mutant is unable to localize to the plasma membrane, it is therefore unable to recruit desmoplakin to sites of cell contact and desmoplakin remains cytosolic in these cells ( Figure 4G).…”

Section: Functional Analysis Of Pkp-2 Mutationsmentioning

confidence: 80%

Arrhythmogenic Right Ventricular Cardiomyopathy Plakophilin-2 Mutations Disrupt Desmosome Assembly and Stability

Hall

et al. 2009

Cell Communication & Adhesion

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Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by lifethreatening ventricular arrhythmias and fibrofatty replacement of the cardiac tissue. Desmosomes are prominent cell-cell junctions found in a variety of tissues that resist mechanical stress, including the heart, and recruit the intermediate filament cytoskeleton to sites of cell-cell contact. Mutations in several desmosomal components including plakophilin-2 have been identified in ARVC patients; however, the molecular interactions disrupted by plakophilin-2 mutations are currently unknown. To understand the pathological basis of ARVC, the authors analyzed desmosome assembly and stability in epithelial cell lines expressing mutants of plakophilin-2 found in ARVC patients. Mutant plakophilin-2 proteins were unable to disrupt established desmosomes when expressed in an E-cadherinÁexpressing epithelial cell model; however, they were unable to initiate de novo assembly of desmosomes in an N-cadherinÁexpressing epithelial cell model. These studies expand our understanding of desmosome assembly and dynamics.

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Section: Functional Analysis Of Pkp-2 Mutationsmentioning

confidence: 80%

Arrhythmogenic Right Ventricular Cardiomyopathy Plakophilin-2 Mutations Disrupt Desmosome Assembly and Stability

Hall

et al. 2009

Cell Communication & Adhesion

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“…Recent studies from the Green lab indicate that PKP2 plays an important role in transport of desmoplakin to the plasma membrane during desmosome assembly. In this model system, PKP2 functions as a scaffold for PKC-a and thereby regulates desmoplakin association with intermediate filaments (Godsel et al 2005;Bass-Zubek et al 2008; see also Green et al 2009). Additional studies will be needed to determine whether PKP1 and PKP3 also regulate assembly through PKC-a.…”

Section: Plakophilinsmentioning

confidence: 99%

The Desmosome

Delva¹,

Tucker²,

Kowalczyk³

2009

Cold Spring Harbor Perspectives in Biology

348

310

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“…The formation of the cytoplasmic plaque appears to be independent of microtubules. Plakophilin 2 (Pkp2) scaffolds desmoplakin and PKC α in a complex together with intermediate fi laments in the cortical region of keratinocytes (Bass-Zubek et al, 2008). The relocation of this complex to the membrane requires a properly organized actin cytoskeleton (Figure 2).…”

Section: Mechanisms Regulating Desmosome Turnovermentioning

confidence: 99%

Desmosomal Cadherins and Signaling: Lessons from Autoimmune Disease

Spindler¹,

Waschke²

2014

Cell Communication & Adhesion

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Autoantibodies from patients suffering from the autoimmune blistering skin disease pemphigus can be applied as tools to study desmosomal adhesion. These autoantibodies targeting the desmosomal cadherins desmoglein (Dsg) 1 and Dsg3 cause disruption of desmosomes and loss of intercellular cohesion. Although pemphigus autoantibodies were initially proposed to sterically hinder desmosomes, many groups have shown that they activate signaling pathways which cause disruption of desmosomes and loss of intercellular cohesion by uncoupling the desmosomal plaque from the intermediate fi lament cytoskeleton and/or by interfering with desmosome turnover. These studies demonstrate that desmogleins serve as receptor molecules to transmit outside-in signaling and demonstrate that desmosomal cadherins have functions in addition to their adhesive properties. Two central molecules regulating cytoskeletal anchorage and desmosome turnover are p38MAPK and PKC. As cytoskeletal uncoupling in turn enhances Dsg3 depletion from desmosomes, both mechanisms reinforce one another in a vicious cycle that compromise the integrity and number of desmosomes.

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Plakophilin 2: a critical scaffold for PKCα that regulates intercellular junction assembly

Cited by 142 publications

References 30 publications

Arrhythmogenic Right Ventricular Cardiomyopathy Plakophilin-2 Mutations Disrupt Desmosome Assembly and Stability

Arrhythmogenic Right Ventricular Cardiomyopathy Plakophilin-2 Mutations Disrupt Desmosome Assembly and Stability

The Desmosome

Desmosomal Cadherins and Signaling: Lessons from Autoimmune Disease

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