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 FRAP and 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 calcium-dependence to calcium-independent hyper-adhesion, their stability increases, but Pkp2a remains highly mobile. We show that desmosome down-regulation during growth-factor-induced cell scattering proceeds by internalisation of whole desmosomes, which still retain a stable moiety and highly mobile Pkp2a. This molecular mobility of Pkp2a suggests a transient and probably regulatory role for Pkp2a in desmosomes.
Desmosome dualism: most of the junction is stable but a plakophilin moiety is persistently dynamic
This work was a collaboration between the research groups of EB Lane, DR Garrod and C Ballestrem.
- Award Group:
- Funder(s): Biotechnology and Biological Sciences Research Council
- Award Id(s): BB/R001707/1
- Funder(s):
- Award Group:
- Funder(s): Wellcome Trust
- Award Id(s): 203128/Z/16/Z
- Funder(s):
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Judith B. Fülle, Henri Huppert, David Liebl, Jaron Liu, Rogerio Alves de Almeida, Bian Yanes, Graham D. Wright, E. Birgitte Lane, David R. Garrod, Christoph Ballestrem; Desmosome dualism: most of the junction is stable but a plakophilin moiety is persistently dynamic. J Cell Sci 2021; jcs.258906. doi: https://doi.org/10.1242/jcs.258906
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