Studies about the metabolic control of daily locomotor behavior in drosophila
- 주제(키워드) metabolism , locomotor
- 주제(DDC) 570
- 발행기관 아주대학교
- 지도교수 김은영
- 발행년도 2022
- 학위수여년월 2022. 2
- 학위명 박사
- 학과 및 전공 일반대학원 의생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000031475
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
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
more목차
I. INTRODUCTION 1
I.1. Circadian clock system 1
I.2. Mechanism of circadian clock system 1
I.3. Metabolism and circadian clock 3
I.4. Aims 6
II. RESULTS 7
II.CHAPTER 1. Metabolic control of daily locomotor activity mediated by tachykinin in Drosophila 7
1. 1. Materials and Methods 7
1. 2. Results 14
1. 2. 1. HSD extended morning activity but not evening activity 14
1. 2. 2. Neuropeptide tachykinin was required for M activity extension in flies on a HSD 21
1. 2. 3. DTk levels were upregulated in DTk neurons in flies on a HSD 30
1. 2. 4. DTk neurons and DN1ps were anatomically and functionally connected 36
1. 2. 5. Subsets of DN1ps were TkR86C positive and required for M activity extension in HSD 52
1. 3. Discussion 57
II. CHAPTER 2. Genetic perturbation of glycolytic pathway altered circadian timekeeping in Drosophila 63
2. 1. Materials and Methods 63
2. 2. Results 67
2. 2. 1. Knockdown of glycolysis rate-limiting enzymes altered circadian rhythm behavior in Drosophila 67
2. 2. 2. Acute knockdown of pyk in LNvs shortened the circadian period 74
2. 2. 3. PDF levels were reduced in pyk knockdown flies 79
2. 2. 4. The TARANIS levels were significantly decreased in tim expressing cells of pyk nockdown flies 86
2. 2. 5. Tara rescued the period shortening from PDF reduction in pyk knockdown flies 90
2. 3. Discussion 100
III.CONCLUSION 105
Iv. REFERENCES 107
v. 국문요약 125
