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김도형,신민정,정성환,Walton D. Jones 한국응용곤충학회 2017 한국응용곤충학회 학술대회논문집 Vol.2017 No.04
동물들은 항상성 유지를 위해서 지방에 축적된 에너지의 양을 판단하고 섭식량을 조절한다고 알려져 있으나 그 조절 메카니즘은 아직 확실히 알려져있지 않다. 본 연구에서는 노랑초파리로 지방세포에서 섭식조절과 관련된 유전자를 찾기 위해 mRNA의 과발현을 이용한 1차 스크리닝(screening)과 RNAi를 이용한 2차 스크리닝을 수행하여 지방세포에서 발현하는 유전자 purple이 섭식조절과 관련이 있다는 것을 확인하였다. 유전자 purple은 조효소인 tetrahydrobiopterin (BH4)의 생합성에 관여하는 유전자인데, 연구결과 BH4생합성에 관련된 다른 유전자인 Punch와 Sepiapterin Reductase (Sptr) 뿐만 아니라 BH4도 섭식행동을 조절하는데에 관여한다는 것을 밝혀냈다. 흥미로운 사실은 Punch와 purple은 지방에서 발현되어야 하는 반면 Sptr은 뇌에서 발현되어 섭식행동을 조절한다는 사실이다. 추가연구를 통해 BH4가 섭식에 관련된 뉴런인 neuropeptide F (NPF)을 억제하여 섭식억제가 이루어지는 사실을 확인하였다. 본 연구는 새로운 유형의 섭식억제제 개발에 기초적인 정보를 제공할 것으로 보인다.
Mass Spectrometry-Based Screening Platform Reveals Orco Interactome in Drosophila melanogaster
Kate E. Yu,김도형,김용인,Walton D. Jones,J. Eugene Lee 한국분자세포생물학회 2018 Molecules and cells Vol.41 No.2
Animals use their odorant receptors to receive chemical information from the environment. Insect odorant recep-tors differ from the G protein-coupled odorant receptors in vertebrates and nematodes, and very little is known about their protein–protein interactions. Here, we introduce a mass spectrometric platform designed for the large-scale analysis of insect odorant receptor protein–protein interactions. Using this platform, we obtained the first Orco interactome from Drosophila melanogaster. From a total of 1,186 identified proteins, we narrowed the interaction candidates to 226, of which only two-thirds have been named. These candidates include the known olfactory proteins Or92a and Obp51a. Around 90% of the proteins having published names likely function inside the cell, and nearly half of these intracellular proteins are associated with the endomembrane system. In a basic loss-of-function electrophysiological screen, we found that the disruption of eight (i.e., Rab5, CG32795, Mpcp, Tom70, Vir-1, CG30427, Eaat1, and CG2781) of 28 randomly selected candidates affects olfactory responses in vivo. Thus, because this Orco interactome includes physiologically meaningful candidates, we anticipate that our platform will help guide further research on the molecular mechanisms of the insect odorant receptor family.
Mass Spectrometry-Based Screening Platform Reveals Orco Interactome in Drosophila melanogaster
Yu, Kate E.,Kim, Do-Hyoung,Kim, Yong-In,Jones, Walton D.,Lee, J. Eugene Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.2
Animals use their odorant receptors to receive chemical information from the environment. Insect odorant receptors differ from the G protein-coupled odorant receptors in vertebrates and nematodes, and very little is known about their protein-protein interactions. Here, we introduce a mass spectrometric platform designed for the large-scale analysis of insect odorant receptor protein-protein interactions. Using this platform, we obtained the first Orco interactome from Drosophila melanogaster. From a total of 1,186 identified proteins, we narrowed the interaction candidates to 226, of which only two-thirds have been named. These candidates include the known olfactory proteins Or92a and Obp51a. Around 90% of the proteins having published names likely function inside the cell, and nearly half of these intracellular proteins are associated with the endomembrane system. In a basic loss-of-function electrophysiological screen, we found that the disruption of eight (i.e., Rab5, CG32795, Mpcp, Tom70, Vir-1, CG30427, Eaat1, and CG2781) of 28 randomly selected candidates affects olfactory responses in vivo. Thus, because this Orco interactome includes physiologically meaningful candidates, we anticipate that our platform will help guide further research on the molecular mechanisms of the insect odorant receptor family.
A Fat-derived metabolite regulates a peptidergic feeding circuit in Drosophila
Do-Hyoung Kim,Minjung Shin,Sung-Hwan Jung,Young-Joon Kim,Walton D. Jones 한국응용곤충학회 2017 한국응용곤충학회 학술대회논문집 Vol.2017 No.10
Animals must maintain proper balance between energy intake and expenditure. Recently, we descovered the enzymaticco-factor tetrahydrobiopterin (BH4) inhibits feeding in Drosophila. BH4 biosynthesis requires the sequential action of theconserved enzymes Punch, Purple, and Sepiapterin Reductase (Sptr). Although we observe increased feeding upon lossof Punch and Purple in the adult fat body, loss of Sptr must occur in the brain. We found Sptr expression is requiredin four adult brain neurons that express NPF, the fly homologue of the vertebrate appetite regulator NPY. Mechanistically,we found BH4 deficiency reduces NPF levels, while excess BH4 increases NPF accumulation without altering its expression.
A fat-derived metabolite regulates a peptidergic feeding circuit in <i>Drosophila</i>
Kim, Do-Hyoung,Shin, Minjung,Jung, Sung-Hwan,Kim, Young-Joon,Jones, Walton D. Public Library of Science 2017 PLoS biology Vol.15 No.3
<▼1><P>Here, we show that the enzymatic cofactor tetrahydrobiopterin (BH4) inhibits feeding in <I>Drosophila</I>. BH4 biosynthesis requires the sequential action of the conserved enzymes Punch, Purple, and Sepiapterin Reductase (Sptr). Although we observe increased feeding upon loss of Punch and Purple in the adult fat body, loss of Sptr must occur in the brain. We found Sptr expression is required in four adult neurons that express neuropeptide F (NPF), the fly homologue of the vertebrate appetite regulator neuropeptide Y (NPY). As expected, feeding flies BH4 rescues the loss of Punch and Purple in the fat body and the loss of Sptr in NPF neurons. Mechanistically, we found BH4 deficiency reduces NPF staining, likely by promoting its release, while excess BH4 increases NPF accumulation without altering its expression. We thus show that, because of its physically distributed biosynthesis, BH4 acts as a fat-derived signal that induces satiety by inhibiting the activity of the NPF neurons.</P></▼1><▼2><P><B>Author summary</B></P><P>As the primary site of energy storage, adipose tissue must somehow monitor energy reserves and communicate this information to the brain. The brain must then modulate feeding behavior to maintain energy balance; however, the mechanisms underlying this communication between fat cells and the brain remain poorly understood. Here, we perform a targeted genetic screen in <I>Drosophila melanogaster</I> and identify a role for the enzymatic cofactor tetrahydrobiopterin (BH4) in regulating ad libitum feeding behavior in fruit flies. We show that three highly conserved enzymes—Punch, Purple, and Sepiapterin Reductase (Sptr)—are required for the biosynthesis of BH4. Fat body-specific knock-down of either Punch or Purple increases feeding, and this increase can be rescued by BH4. We find that rather than also being required in the fat body, Sptr is required in brain neurons that express neuropeptide F (NPF), the fly homologue of the vertebrate appetite regulator neuropeptide Y (NPY). BH4 also rescues the increase in feeding caused by NPF neuron-specific knock-down of Sptr. Although the exact mechanism remains unclear, our results suggest that BH4 inhibits signaling through NPF neurons by blocking their release of NPF. Based on its novel function in feeding and its physically distributed biosynthesis, BH4 may, therefore, represent one of the elusive signals that communicates energy status from the adipose tissue to the brain.</P></▼2>
Identification of a Peptidergic Pathway Critical to Satiety Responses in Drosophila
Min, S.,Chae, H.S.,Jang, Y.H.,Choi, S.,Lee, S.,Jeong, Y.,Jones, Walton D.,Moon, S.,Kim, Y.J.,Chung, J. Current Biology Ltd ; Elsevier Science Ltd 2016 Current biology Vol.26 No.6
<P>Although several neural pathways have been implicated in feeding behaviors in mammals [1-7], it remains unclear how the brain coordinates feeding-motivations to maintain a constant body weight (BW). Here, we identified a neuropeptide pathway important for the satiety and BW control in Drosophila. Silencing of myoinhibitory peptide (MIP) neurons significantly increased BW through augmented food intake and fat storage. Likewise, the loss-offunction mutation of mip also increased feeding and BW. Suppressing the MIP pathway induced satiated flies to behave like starved ones, with elevated sensitivity toward food. Conversely, activating MIP neurons greatly decreased food intake and BW and markedly blunted the sensitivity of starved flies toward food. Upon terminating the activation protocol of MIP neurons, the decreased BW reverts rapidly to the normal level through a strong feeding rebound, indicating the switch-like role of MIP pathway in feeding. Surprisingly, the MIP-mediated BW decrease occurred independently of sex peptide receptor (SPR), the only known receptor for MIP, suggesting the presence of a yet-unknown MIP receptor. Together, our results reveal a novel anorexigenic pathway that controls satiety in Drosophila and provide a new avenue to study how the brain actively maintains a constant BW.</P>