Circadian timing of the dystrophin associated complex across the brain and body

The dystrophin associated complex (DAC) is an integral membrane scaffold that regulates cellular polarization and structural organization in both brain and peripheral tissues. In the brain, the DAC anchors the water channel aquaporin 4 (AQP4) to astrocytic vascular endfeet, thereby supporting glymphatic waste clearance during the inactive phase. Recent studies have raised the question of whether DAC gene expression is under circadian control. By mining four independent circadian transcriptome and translatome databases, covering multiple brain regions, peripheral tissues, ages, and species, we show that both Aqp4 and the DAC components exhibit circadian rhythms in gene expression across most of the brain and body in mice, chickens and baboons. In addition, Aqp1 shows circadian rhythmicity in peripheral tissues. The phase of these rhythms varies by tissue type yet collectively supports the hypothesis that clock-regulated DAC activity represents a conserved mechanism for coordinating ion, water, and structural homeostasis throughout the body.