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Studies about the metabolic control of daily locomotor behavior in drosophila
- Author(s)
- 이상혁
- Alternative Author(s)
- Sang Hyuk Lee
- Advisor
- 김은영
- Department
- 일반대학원 의생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2022-02
- Language
- eng
- Keyword
- locomotor; metabolism
- Alternative Abstract
- The circadian clock system allows living organisms to adapt to environmental changes, resulting in ~24 h rhythms of behavior and physiology. Many metabolic processes, e.g., glucose, protein and lipid metabolism are regulated by the circadian clock; in turn, there is evidence that the circadian clock system is affected by metabolic signals such as NAD+, ATP and O-GlcNAcylation. Although significant progress has been made in the crosstalk between metabolism and the circadian clock, the understanding is yet complete. In this thesis, I investigated the mechanism via which glucose metabolism affects the circadian clock by examining the circadian rhythm behavior of Drosophila melanogaster exposed to metabolic perturbation and the mechanism underlying the control of this behavior. Drosophila maintained in a high-nutrient diet showed extended morning (M) activity, but not evening (E) activity. Enhanced Drosophila tachykinin (DTk)- and tachykinin-like receptor at 86C-mediated signaling was required for the extension of M activity. DTk neurons were anatomically and functionally connected to posterior dorsal neuron 1s (DN1ps) in the core clock neuronal network. The activation of DTk neurons reduced the intracellular Ca2+ levels in DN1ps, which was suggestive of an inhibitory connection. The contacts between DN1ps and DTk neurons increased gradually over time in flies that were fed a highsucrose diet, which was consistent with the locomotor behavior. DN1ps have been implicatedii in the integration of environmental sensory input, e.g., light and temperature to control daily locomotor behavior. This study revealed that DN1ps also coordinated nutrient information through DTk signaling to shape daily locomotor behavior. Adult-specific knockdown of the pyruvate kinase (pyk), which is the rate-limiting enzyme of glycolysis in clock cells, shortened the circadian rhythm period. Lateral ventral neuron (LNvs) specific knockdown of pyk shortened period but glia specific knockdown did not affect period. The pigment dispersing factor (PDF), which is selectively expressed in LNvs, synchronizes the circadian neuronal network and controls circadian rhythm behavior. The intensity of PDF expression was greatly reduced in pyk knockdown flies. Interestingly, the level of TARANIS (TARA), which is a Drosophila homolog of the Trip-Br (Transcriptional Regulators Interacting with PHD zinc fingers and/or bromodomains) family of transcriptional coregulators proteins, was reduced in pyk knockdown flies. Overexpression of tara rescued the short period of pyk knockdown flies and PDF levels were restored to normal levels. Taken together, these results suggest that TARA recognizes the cellular metabolic status and modulates the circadian rhythm by regulating the levels of PDF expression
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Biomedical Sciences > 4. Theses(Ph.D)
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