A genetic RNAi screen for IP₃/Ca²⁺ coupled GPCRs in Drosophila identifies the PdfR as a regulator of insect flight.
A genetic RNAi screen for IP₃/Ca²⁺ coupled GPCRs in Drosophila identifies the PdfR as a regulator of insect flight.
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DOI：
10.1371/journal.pgen.1003849
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Hasan G
中科院分区：
文献类型：
--
作者：
Agrawal T;Sadaf S;Hasan G
Insect flight is regulated by various sensory inputs and neuromodulatory circuits which function in synchrony to control and fine-tune the final behavioral outcome. The cellular and molecular bases of flight neuromodulatory circuits are not well defined. In Drosophila melanogaster, it is known that neuronal IP3 receptor mediated Ca2+ signaling and store-operated Ca2+ entry (SOCE) are required for air-puff stimulated adult flight. However, G-protein coupled receptors (GPCRs) that activate intracellular Ca2+ signaling in the context of flight are unknown in Drosophila. We performed a genetic RNAi screen to identify GPCRs that regulate flight by activating the IP3 receptor. Among the 108 GPCRs screened, we discovered 5 IP3/Ca2+ linked GPCRs that are necessary for maintenance of air-puff stimulated flight. Analysis of their temporal requirement established that while some GPCRs are required only during flight circuit development, others are required both in pupal development as well as during adult flight. Interestingly, our study identified the Pigment Dispersing Factor Receptor (PdfR) as a regulator of flight circuit development and as a modulator of acute flight. From the analysis of PdfR expressing neurons relevant for flight and its well-defined roles in other behavioral paradigms, we propose that PdfR signaling functions systemically to integrate multiple sensory inputs and modulate downstream motor behavior. A majority of behavioral patterns in flying insects depend upon their ability to modulate flight. In Drosophila melanogaster, mutations in the IP3 receptor gene lead to loss of voluntary flight in response to a natural stimulus like a gentle air-puff. From previous genetic and cellular studies it is known that the IP3R in Drosophila is activated by G-protein coupled receptors (GPCRs). However, GPCRs that act upstream of the IP3R in the context of flight are not known. Therefore, we performed a genetic RNAi screen to identify GPCRs which regulate flight. This screen was followed by a secondary suppressor screen that assessed the role of each identified GPCR in activating IP3/Ca2+ signaling. We found 5 such GPCRs. Our results demonstrate that these GPCRs are required during flight circuit development and during adult flight. One flight-regulating receptor identified was the Pigment Dispersing Factor Receptor (PdfR). This receptor is known to regulate behaviors such as circadian rhythms, geotaxis and reproduction. A spatio-temporal analysis of PdfR flight function indicates that it regulates both flight circuit development and acute flight through multiple neurons. We postulate that PdfR signaling could modulate and integrate multiple behavioral inputs in Drosophila and other flying insects.
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DOI：
10.1083/jcb.150.2.f83
发表时间：
2000-07-24
期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
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影响因子：
56.9
作者：
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影响因子：
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影响因子：
11.4
作者：
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DOI：
10.1002/cne.22311
发表时间：
2010-06-01
期刊：
The Journal of comparative neurology
影响因子：
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作者：
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通讯作者：
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