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bioRxiv · 10.1101/2021.03.02.433631

Desmosomal dualism: the core is stable while plakophilin is dynamic.

Fulle, J. B.·Huppert, H.·Liebl, D.·Liu, J.·Alves de Almeida, R.·Yanes, B.·Wright, G. D.·Lane, E. B.·Garrod, D. R.·Ballestrem, C.
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Abstract

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 5 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 fractions or modules: a very stable desmosomal core of desmosomal cadherins and plakoglobin, and a highly mobile plakophilin. As desmosomes mature from calcium-dependence to calciumindependent hyper-adhesion, core stability increases, but Pkp2a remains highly mobile. Desmoplakin is initially mobile but stabilises with hyper-adhesion. We show that desmosome down-regulation during growth factor-induced cell scattering proceeds by internalisation of whole desmosomes, which still retain a stable core and highly mobile Pkp2a. This molecular mobility of Pkp2a suggests a transient and probably regulatory role for Pkp2a in the desmosome.

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Fulle, J. B., Huppert, H., Liebl, D., Liu, J., Alves de Almeida, R., Yanes, B., Wright, G. D., Lane, E. B., Garrod, D. R., Ballestrem, C.. 2021-03-02. Desmosomal dualism: the core is stable while plakophilin is dynamic.. https://doi.org/10.1101/2021.03.02.433631

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