The Case for the Target of Rapamycin Pathway as a Candidate Circadian Oscillator.

The molecular mechanisms that drive circadian (24 h) rhythmicity have been investigated for many decades, but we still do not have a complete picture of eukaryotic circadian systems. Although the transcription/translation feedback loop (TTFL) model has been the primary focus of research, there are many examples of circadian rhythms that persist when TTFLs are not functioning, and we lack any good candidates for the non-TTFL oscillators driving these rhythms. In this hypothesis-driven review, the author brings together several lines of evidence pointing towards the Target of Rapamycin (TOR) signalling pathway as a good candidate for a non-TTFL oscillator.

Shared Components of the FRQ-Less Oscillator and TOR Pathway Maintain Rhythmicity in .

Molecular models for the endogenous oscillators that drive circadian rhythms in eukaryotes center on rhythmic transcription/translation of a small number of "clock genes." Although substantial evidence supports the concept that negative and positive transcription/translation feedback loops (TTFLs) are responsible for regulating the expression of these clock genes, certain rhythms in the filamentous fungus continue even when clock genes (, , and ) are not rhythmically expressed. Identification of the rhythmic processes operating outside of the TTFL has been a major unresolved area in circadian biology.

Circadian rhythms, metabolic oscillators, and the target of rapamycin (TOR) pathway: the Neurospora connection.

Circadian (24-h) rhythmicity is a fundamental property of eukaryotic cells, and it is not surprising that it intersects with fundamental metabolic processes. Many links between these two processes have been documented, and speculation has been growing that there may be circadian "metabolic oscillators" that interact with and exist independently of the well-known circadian transcription/translation feedback loops (TTFLs) that have been extensively studied. This review takes a critical look at the evidence for the existence of metabolic oscillators at the cellular level, attempting to answer these questions: does metabolism affect circadian rhythmicity, and vice versa? Is metabolism rhythmic, and if so, is that rhythmicity cell autonomous? Systems displaying "non-canonical rhythmicity" in the absence of functional TTFLs provide opportunities for identifying metabolic oscillators, and this review emphasizes the fungus Neurospora crassa as a model system.

A component of the TOR (Target Of Rapamycin) nutrient-sensing pathway plays a role in circadian rhythmicity in Neurospora crassa.

The TOR (Target of Rapamycin) pathway is a highly-conserved signaling pathway in eukaryotes that regulates cellular growth and stress responses. The cellular response to amino acids or carbon sources such as glucose requires anchoring of the TOR kinase complex to the lysosomal/vacuolar membrane by the Ragulator (mammals) or EGO (yeast) protein complex. Here we report a connection between the TOR pathway and circadian (daily) rhythmicity.

PRD-1, a Component of the Circadian System of Neurospora crassa, Is a Member of the DEAD-box RNA Helicase Family.

The circadian rhythms found in almost all organisms are driven by molecular oscillators, including transcription/translation feedback loops (TTFLs). However, TTFL-independent oscillators can drive rhythms in both eukaryotes and prokaryotes. The fungus Neurospora crassa is a model organism for studying the molecular mechanism of the circadian clock.