Endoplasmic/sarcoplasmic reticulum Ca2+ stores are essential to myriad cellular processes, however, the structure of these stores is largely unknown and existing models neither explain observations made in vivo nor sufficiently account for physiological data. 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 novel 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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ABSTRACT. The liver has extraordinary powers of regeneration following partial hepatectomy (PH). Changes in gene expression levels play a key role in cell proliferation and differentiation during liver regeneration (LR). To understand the molecular mechanisms underlying LR, this study was designed to assess the time-dependent changes in rat hepatic gene expression. We obtained a gene expression profile of rat LR with high temporal resolution. We then constructed gene co-expression networks of regenerating liver tissue and identified 13 LR-specific modules from 1772 differentially expressed genes, and prioritized signaling pathways that regulated LR after PH. The results indicated that adipocytokine signaling, histone acetylation, and IL-6-related pathways play an important role in LR. Co-expression network analysis provides novel insight into understanding the molecular mechanisms behind LR.