Abstract
Desmosomes are intercellular junctions that anchor intermediate filaments (IFs) to the plasma membrane, forming a supracellular scaffold that provides mechanical resilience to tissues. This anchoring function is accomplished by specialized members of the cadherin family and associated cytoskeletal linking proteins, which together form a highly organized membrane core flanked by mirror-image cytoplasmic plaques. Due to the biochemical insolubility of desmosomes, the mechanisms that govern assembly of these components into a functional organelle remained elusive. Recently developed molecular reporters and live cell imaging approaches have provided powerful new tools to monitor this finely tuned process in real time. Here we discuss studies that are beginning to decipher the machinery and regulation governing desmosome assembly and homeostasis in situ and how these mechanisms are affected during disease pathogenesis.
🔬 Techniques
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🧪 Sample Preparation
🔬 Cell Lines
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💾 Data Repositories
🏛️ Research Organizations (ROR)
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📊 Figures
Figure 1
Structure and positioning of desmosomal proteins: cadherins, armadillo proteins and desmoplakin
Desmosomal cadherins, desmogleins (Dsg) and desmocollins (Dsc), share similar architecture each containing extracellular cadherin domains (ECs 1u20134) that link via an extracellular anchor (EA) and m...
Figure 2
Model of possible molecular dynamics of membrane pool assembly
Desmoglein and desmocollin containing vesicles emerge from the Golgi and are transported along microtubules utilizing kinesin-1 or kinesin-2 respectively. The kinesins deliver desmosomal cadherins to ...
Figure 3
Model of molecular dynamics of cytoplasmic pool assembly
E-cadherin initiates the assembly of the cytoplasmic plaque, possibly by recruiting Pg-PKP2 or Pg-PKP3 complexes to the plasma membrane, which in turn recruit the free pool of desmoplakin to the cell ...
Figure 4
Scheme of DP-related signaling events that regulate desmosome assembly and remodeling.
Figure 5
Defects in desmosome assembly that been observed in different human pathologies, highlighting the desmogleins (Dsg)
Mutations can lead to protein misfolding and prevent proper translocation or assembly into mature desmosomes, resulting in internalization (A). Serum autoantibodies (PF-IgG) can react with the N termi...
Figure images are served from the NIH/NLM PubMed Central Open Access Subset or Europe PMC; copyright remains with the publishers and authors.
💬 Discussion
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