Desmosomes are intercellular junctions that anchor intermediate filaments to the plasma membrane. Ultrastructural studies of desmosomes have proved challenging owing to their size, insolubility and molecular complexity, but super-resolution fluorescence microscopy offers a solution. In their Short Report on page , Alexa Mattheyses and colleagues use super-resolution direct stochastic optical reconstruction microscopy (dSTORM) to investigate protein organisation within the desmosome at the molecular level. The authors show that dSTORM can resolve proteins in both the outer and inner dense plaques in individual desmosomes. Using domain-specific antibodies, the authors apply dSTORM to map the molecular arrangement of desmoglein 3, plakoglobin and desmoplakin in human keratinocytes, and find a trend of increasing demosome length with increasing distance from the plasma membrane. Moreover, desmoplakin appears to be oriented at an angle in the plaque. Importantly, the authors show that different desmosomal adhesive states change plaque organisation, suggesting that protein reorganisation within the desmosomal plaque correlates with changes in adhesive strength. Finally, the authors show that desmosome molecular organisation is conserved in skin, demonstrating that their approach can also be applied to human tissue sections. This study is a convincing demonstration of the power of dSTORM to resolve desmosomal architecture at the molecular level.
