EVIDENCE AGAINST A DIRECT ROLE FOR INOSITOL PHOSPHATE-METABOLISM IN THE CIRCADIAN OSCILLATOR AND THE BLUE-LIGHT SIGNAL-TRANSDUCTION PATHWAY IN NEUROSPORA-CRASSA

The inositol-depletion hypothesis proposes that the effects of Li+ on cellular functions are the result of inhibition by Li+ of the inositol monophosphate phosphatase and subsequent depletion of inositol lipids. This mechanism has been proposed to account for the effects of Li+ on the period of the circadian oscillator. Inositol phosphate metabolism has also been proposed as part of the blue-light signal-transduction pathway through which the phase of the circadian oscillator can be reset by light pulses. Four predictions of these two hypotheses have been tested in the fungus Neurospora crassa and all have been found to fail: (1) inositol supplementation does not reverse the effects of Li+ on the period of the circadian rhythm; (2) inositol depletion of an inositol-requiring mutant does not mimic the effects of Li+; (3) depletion of inositol lipids does not inhibit the response to light; and (4) a phase-resetting pulse of light does not increase the levels of inositol phosphates, including Ins(1,4,5)P3.