Ca2+-dependent liquid-liquid phase separation underlies intracellular Ca2+ stores.

Mayfield, J. E.; Pollak, A. J.; Worby, C. A.; Xu, J. C.; Tandon, V.; Newton, A. C.; Dixon, J. E.

doi:10.1101/2021.07.06.451223

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bioRxiv · 10.1101/2021.07.06.451223

Ca2+-dependent liquid-liquid phase separation underlies intracellular Ca2+ stores.

Mayfield, J. E.·Pollak, A. J.·Worby, C. A.·Xu, J. C.·Tandon, V.·Newton, A. C.·Dixon, J. E.

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Abstract

Endoplasmic/sarcoplasmic reticulum Ca2+ stores are essential to myriad cellular processes, however, the structure of these stores is largely unknown and existing models do not address all literature observations. We investigate CASQ1 - the major Ca2+ binding protein of skeletal muscle - and discover Ca2+-dependent liquid-liquid phase separation activity. The intrinsic disorder of CASQ1 underlies this activity and is regulated via phosphorylation by the secretory pathway kinase FAM20C. This divalent cation driven condensation demonstrates liquid-liquid phase separation occurs within the endoplasmic/sarcoplasmic reticulum, mechanistically explains efficient Ca2+ buffering and storage, and represents a largely unexplored mechanism of divalent-cation driven protein association.

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Mayfield, J. E., Pollak, A. J., Worby, C. A., Xu, J. C., Tandon, V., Newton, A. C., Dixon, J. E.. 2021-07-06. Ca2+-dependent liquid-liquid phase separation underlies intracellular Ca2+ stores.. https://doi.org/10.1101/2021.07.06.451223

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