cAMP and a Retinal Clock

In photoreceptors, an autonomous circadian clock interacts with the light/dark cycle to control aspects of retinal function. The circadian pattern of melatonin synthesis in photoreceptors is regulated by arylalkylamine N-acetyltransferase (AANAT). Transcription of AA-NAT is under dual control by CLOCK and BMAL1 transcription factors at an E-box transcriptional site, and by a cAMP:cAMP response element (CRE)-mediated site. Fukuhara et al. now report that the gene for type 1 adenylyl cyclase (AC1) also contains an E-box site, and it too is controlled by the CLOCK:BMAL1 complex. The clock genes exerted rhythmic control of AC1 expression, and thus cAMP synthesis, in the retina as well as in the pineal gland and suprachiasmatic nucleus. Because AC1 is calcium dependent, the nighttime increase in photoreceptor cytoplasmic calcium, induced by the depolarizing dark current, increases cAMP and thus melatonin synthesis. The authors suggest that clock control of cAMP signaling may serve a general role in the integration of circadian signals.