The peculiar dualism of desmosome dynamics.

Session

Multimodal Microscopy

Authors

Dr Judith B. Fülle (4), Dr Henri Huppert (4), Dr David Liebl (1), Dr Jaron Liu (2), Dr Rogerio Alves de Almeida (4), Ms Bian Yanes (4), Dr Graham D. Wright (3), Dr E. Birgitte Lane (3), Dr David R. Garrod (4), Dr Christoph Ballestrem (4)

Affiliations

1. A*STAR Microscopy Platform, Research Support Centre, Agency of Science Technology and Research (A*STAR)
2. Institute of Medical Biology, Agency of Science Technology and Research (A*STAR)
3. Skin Research Institute of Singapore, Agency of Science Technology and Research (A*STAR)
4. Wellcome Trust Centre for Cell-Matrix Research, University of Manchester

Keywords

Cell-cell junctions, desmosomes, plakophilin, dynamics, hyper-adhesion

Abstract text

Desmosomes, strong cell–cell junctions of epithelia and cardiac muscle, link intermediate filaments to cell membranes and mechanically integrate cells across tissues, dissipating mechanical stress. They comprise five major protein classes - desmocollins and desmogleins (the desmosomal cadherins), plakoglobin, plakophilins and desmoplakin - whose individual contribution to the structure and turnover of desmosomes is poorly understood. Using live-cell imaging together with fluorescence recovery after photobleaching (FRAP) and fluorescence loss and localisation after photobleaching (FLAP), we show that desmosomes consist of two contrasting protein moieties or modules: a very stable moiety of desmosomal cadherins, desmoplakin and plakoglobin, and a highly mobile plakophilin (Pkp2a). As desmosomes mature from Ca²⁺ dependence to Ca²⁺-independent hyper-adhesion, their stability increases, but Pkp2a remains highly mobile. Furthermore, using correlative light and electron microscopy (CLEM) and structured illumination microscopy (SIM) we show that desmosome downregulation during growth-factor-induced cell scattering proceeds by internalisation of whole desmosomes. These internalised double-plaque-bearing desmosomes retain a stable moiety and highly mobile Pkp2a. This molecular mobility of Pkp2a suggests a transient and probably regulatory role for Pkp2a in desmosomes.

References

Fülle, J.B., H. Huppert, D. Liebl, J. Liu, R.A. de Almeida, B. Yanes, G.D. Wright, E.B. Lane, D.R. Garrod, and C. Ballestrem. 2021. Desmosome dualism: most of the junction is stable but a plakophilin moiety is persistently dynamic. Journal of Cell Science. doi:10.1242/jcs.258906.