Abstract

The circadian clock is an endogenous mechanism synchronising the timing of biological processes with daily fluctuations in the environment. Previous work in the lab has demonstrated that in Arabidopsis thaliana, [Ca2+]cyt participates in a feedback loop within the clock, mediated by the Ca2+-releasing agent cyclic adenosine diphosphate ribose (cADPR). cADPR is synthesised from nicotinamide adenine dinucleotide (NAD+) by the enzyme ADPR cyclase, releasing nicotinamide as a by-product. Nicotinamide treatment abolishes circadian oscillations of [Ca2+]cyt and lengthens the period of other clock outputs by inhibiting ADPR cyclase.

PAR Ps and sirtuins are other classes of enzymes which also consume NADplus and are inhibited by nicotinamide. We are investigating which of these pathways is responsible for the connection to circadian signalling, and is the target of nicotinamide with respect to the clock. We are testing the hypothesis that alterations in NADplus levels, and consequently cADPR, results in altered clock behaviour due to disturbed [Ca2+]cyt rhythms, therefore coupling NAD + metabolism and the circadian clock.