Phosphorylation and Lamin B receptor modulate the accumulation of PERIOD protein foci

Abstract

Circadian clock drives the 24h rhythm in our behavior and physiology. Previously, we have shown that inner nuclear membrane protein Lamin B receptor (LBR) regulates circadian rhythm in human cells and Drosophila, while the underlying mechanism is unclear (Lin et al., 2014). A very recent study reported that the circadian clock protein PERIOD is organized into discrete foci at the nuclear envelope in fly circadian neurons, which is believed to be important for controlling the subcellular localization of clock genes. Loss of LBR leads to disruption of these foci, but how they are regulated is yet unknown. Here we found that LBR likely facilitates PER foci accumulation by destabilizing the catalytic subunit of protein phosphatase 2A, MICROTUBULE STAR (MTS). MTS is known to dephosphorylate PER and hampers the accumulation of PER foci. On the other hand, the circadian kinase DOUBLETIME (DBT) which phosphorylates PER enhances the accumulation of the foci. These foci are likely phase-separated condensates, the formation of which mediated by intrinsically disordered region in PER. Taken together, here we demonstrate a key role for phosphorylation in promoting the accumulation of PER foci, while LBR modulates this process by impinging on the circadian phosphatase MTS.