Role of the Rh01 GTPase signaling pathway in regulating the circadian clock in Drosophila melanogaster

Virtually every biological function is influenced by the time of the day and the mechanisms that control circadian rhythmicity stand at the intersection of multiple pathways. In fruit flies, circadian rhythms are molecularly generated by a set of interlocking transcriptional and translational feedback loops. The timing and sequence of events in these loops are tightly controlled by regulatory proteins, and are dependent on constitutive cellular functions to ensure robustness. Circadian rhythmicity can both affect these constitutive processes as well as be influenced by their associated dynamics. Very little is known however, about the mechanisms by which these interactions occur and this is a subject of increasing interest. This dissertation work examines the consequences of RHO1 GTPase signaling to the cellular cytoskeleton for circadian rhythms in fruit flies. A systematic genetic screen identified Rho] as a candidate gene involved in regulating circadian behavior. Transgenic knockdown of RHO1 and its upstream or downstream effectors, confirmed that the entire GTPase signaling pathway has a role in modifying circadian behavior. This effect was not associated with gross cytoskeletal defects such as cell death, changes in neuroanatomy, or with developmental functions of RHO1 signaling. Instead, RHO1 signaling via its effector RHO KINASE (ROK) can specifically and cell-autonomously alter oscillator function in a small group of pacemaker neurons in the adult fly brain.

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