The Novel Drosophila timblind Mutation Affects Behavioral Rhythms but Not Periodic Eclosion

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Abstract
Circadian clock function depends on the tightly regulated exclusion or presence of clock proteins within the nucleus. A newly induced long-period timeless mutant, timblind, encodes a constitutively hypophosphorylated TIM protein. The mutant protein is not properly degraded by light, and timblind flies show abnormal behavioral responses to light pulses. This is probably caused by impaired nuclear accumulation of TIMBLIND protein, which we observed in brain pacemaker neurons and photoreceptor cells of the compound eye. timblind encodes two closely spaced amino acid changes compared to the wild-type TIM protein; one of them is within a putative nuclear export signal of TIM. Under constant conditions, timblind flies exhibit 26-hr free-running locomotor rhythms, which are not correlated with a period lengthening of eclosion rhythms and period-luciferase reporter-gene oscillations. Therefore it seems possible that TIM—in addition to its well-established role as core clock factor—functions as a clock output factor, involved in determining the period length of adult locomotor rhythms.