Measuring the Levels and Activity of the Key Body Clock Protein PERIOD2 Inside Cells

A knockin mouse expressing a fluorescent fusion of native PER2 protein (PER2::VENUS) provides new insights into the behavior of circadian proteins in mammals.

• PER2::VENUS accurately reflects the circadian functions of wild-type PER2.
• The behavior of PER2::VENUS contradicts the Drosophila model, as it does not show circadian gating of nuclear entry.
• Fluorescent imaging revealed the first measures of mobility, molecular concentration, and localization of an endogenous circadian protein in mammalian cells.
• Mobility and nuclear translocation of PER2 are regulated by casein kinase.
• These findings offer new qualitative and quantitative insights into the cellular mechanisms underlying the mammalian circadian clock.

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