A putative role for TANGO in the circadian clock of Drosophila melanogaster

Living organisms can anticipate predictable environmental cycles using self-sustained pacemakers found in the brain and in a variety of tissues. This internal clock generates rhythms that can persist even in the absence of environmental time cues. For the circadian clock to be functional it must have the ability to entrain, i.e. to respond to environmental cues such as the 24 h light-dark cycle. The clock mechanism involves negative feedback loops associated with daily oscillations of several genes expression at both the RNA and protein levels. The mammalian Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) homologous gene tango (tgo) is essential for normal Drosophila melanogaster development. TANGO (TGO) is a transcription factor, which belongs to the PAS (Per-Arnt-Sim) superfamily and, in the yeast-two-hybrid system, physically interacts with the circadian proteins CLOCK (CLK) and CRYPTOCHROME (CRY), suggesting a possible role for tgo in the circadian clock. Miss-expression of tgo does not interfere with the 24h period of locomotor activity but causes abnormal behavioural responses to light. However, the generalised reduction of TGO promotes an internal desynchronization between the morning and evening clock oscillators, suggesting that TGO might be involved in neuronal crosstalk. Moreover, miss-expression of tgo seems to promote an advance in the phase of expression of the TIMELESS protein, a key regulator of circadian light-responses in Drosophila. Finally, TGO was shown to be involved in sleep regulation, as revealed by a reduction in the amount of sleep in flies overexpressing or down-regulating this protein. In conclusion, this study indicates that TGO does not control the inner molecular cogs of the clock but strongly suggests a potential function for TGO in the input and/or output mechanisms and also a role in the sleep regulation process.