Desmoplakin and clinical manifestations of desmoplakin cardiomyopathy

Figures

• 

  Figure 1. The structure of DSP. The three isoforms differ in the length of the central rod domain (Rod). The C-Tail contains three PRDs (A–C) and a GSR domain that is thought to regulate DSP binding to IFs. The amino-terminal globular head domain (Head) mediates protein–protein interactions. C-Tail: Carboxy-terminal tail; GSR: Glycine–serine–arginine rich; DSP: Desmoplakin; IF: Intermediate filaments; PRDs: Plakin repeat domains.

• 

  Figure 2. The relative position of DSP in desmosome. The DSGs and DSCs extend into the extracellular core and ODP to establish, contact, and adhere to neighboring cells. Cadherin cytoplasmic tails associate with linker proteins, PKG, PKP, and DSP. DSP binds IF within the IDP, serving to tether the IF to the PM. DSC: Desmocollin; DSG: Desmoglein; DSP: Desmoplakin; IDP: Inner dense plaque; IF: Intermediate filaments; ODP: Outer dense plaque; PKG: Plakoglobin; PKP: Plakophilin; PM: Plasma membrane.

• 

  Figure 3. The Wnt/β-catenin pathway. When PKG translocates from desmosomes to the nucleus, it competes with β-catenin for binding to the TCF7L2/LEF1 transcription factors, leading to suppression of the Wnt pathway, which means an increase in adipogenesis and fibrosis and adipogenesis and a decrease in myogenesis. GSK3β: Glycogen synthase kinase-3 beta; PKG: Plakoglobin; TCF/LEF: T-cell factor/lymphoid enhancer factor.

• 

  Figure 4. The Hippo/YAP pathway. Activated Hippo pathways and suppressed YAP signaling leads to an increase in apoptosis as well as Wnt/β-catenin pathway suppression through interactions between YAP and β-catenin in the nucleus, and pYAP-mediated sequestration of β-catenin in the cytosol. LATS1/2: Large tumor suppressor kinases 1/2; MST1/2: Mammalian STE20-like protein kinases 1/2; TEAD: Transcriptional enhancer factor domain; YAP: Yes-associated protein.