Desmosome dualism - most of the junction is stable, but a plakophilin moiety is persistently dynamic.

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

Journal of cell science 2021 Nov 01

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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. We show that desmosome downregulation 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. This article has an associated First Person interview with the first author of the paper. © 2021. Published by The Company of Biologists Ltd.

Citation

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. Journal of cell science. 2021 Nov 01;134(21)