Reference Report

Reference
Citation	Duvall, L.B., Taghert, P.H. (2012). The Circadian Neuropeptide PDF Signals Preferentially through a Specific Adenylate Cyclase Isoform AC3 in M Pacemakers of Drosophila. PLoS Biol. 10(6): e1001337. (Export to RIS)
FlyBase ID	FBrf0218594
Publication Type	Research paper
PubMed ID	22679392
PubMed Abstract	The neuropeptide Pigment Dispersing Factor (PDF) is essential for normal circadian function in Drosophila. It synchronizes the phases of M pacemakers, while in E pacemakers it decelerates their cycling and supports their amplitude. The PDF receptor (PDF-R) is present in both M and subsets of E cells. Activation of PDF-R stimulates cAMP increases in vitro and in M cells in vivo. The present study asks: What is the identity of downstream signaling components that are associated with PDF receptor in specific circadian pacemaker neurons? Using live imaging of intact fly brains and transgenic RNAi, we show that adenylate cyclase AC3 underlies PDF signaling in M cells. Genetic disruptions of AC3 specifically disrupt PDF responses: they do not affect other Gs-coupled GPCR signaling in M cells, they can be rescued, and they do not represent developmental alterations. Knockdown of the Drosophila AKAP-like scaffolding protein Nervy also reduces PDF responses. Flies with AC3 alterations show behavioral syndromes consistent with known roles of M pacemakers as mediated by PDF. Surprisingly, disruption of AC3 does not alter PDF responses in E cells--the PDF-R(+) LNd. Within M pacemakers, PDF-R couples preferentially to a single AC, but PDF-R association with a different AC(s) is needed to explain PDF signaling in the E pacemakers. Thus critical pathways of circadian synchronization are mediated by highly specific second messenger components. These findings support a hypothesis that PDF signaling components within target cells are sequestered into "circadian signalosomes," whose compositions differ between E and M pacemaker cell types.
DOI	10.1371/journal.pbio.1001337
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Language of Publication	English
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Publication Type	Journal
Abbreviation	PLoS Biol.
Title	PLoS Biology
Publication Year	2003-
ISBN/ISSN	1545-7885 1544-9173
Data from Reference
Aberrations (1)
	Df(2L)DS6
Alleles (32)
	Ac3^GD1799 Ac3^JF03041 Ac3^Scer\UAS.cDa Ac13E^GD3374 Ac76E^GD2737 Ac76E^Scer\UAS.cDa Ac78C^GD2764 Ac78C^Scer\UAS.cDa ACXA^KK107022 ACXB^KK106308 ACXC^KK103168 ACXD^KK106797 ACXD^Scer\UAS.cDa Akap200^HM05018 Avic\GFP^{Epac1-camps.Scer\UAS} CG32301^GD3573 CG32305^KK106912 Dh31-R1^Scer\UAS.cDa Gαs^KK107742 Gαs^Scer\UAS.cCa nvy^JF03349 Pdf⁰¹ Pdfr⁵³⁰⁴ Pdfr^Scer\UAS.cMa Pdfr^T:Hsap\MYC rg^KK102295 rut^GD3358 rut^Scer\UAS.cZa Scer\GAL4^Mai179 Scer\GAL4^P2.4.Pdf Scer\GAL80^ts.αTub84B spoon^KK101210
Constructs (29)
	P{GD1799} P{GD2737} P{GD2764} P{GD3358} P{GD3374} P{GD3573} P{KK101210} P{KK102295} P{KK103168} P{KK106308} P{KK106797} P{KK106912} P{KK107022} P{KK107742} P{Pdf-GAL4.P2.4} P{Pdfr-myc} P{TRiP.HM05018} P{TRiP.JF03041} P{TRiP.JF03349} P{tubP-GAL80^ts} P{UAS-Ac3.D} P{UAS-Ac76E.D} P{UAS-Ac78C.D} P{UASACXD-.D} P{UAS-Dh31-R1.D} P{UAS-Epac1-camps} P{UAS-G-sα60A.C} P{UAS-pdfr.M} P{UAS-rut.Z}
Genes (23)
	Ac3 Ac13E Ac76E Ac78C ACXA ACXB ACXC ACXD Akap200 Avic\GFP CG32301 CG32305 Dh31 Dh31-R1 Gαs nvy Pdf Pdfr rg rut Scer\GAL4 Scer\GAL80 spoon
Insertions (1)
	P{GawB}l(2)Mai179^Mai179
Natural transposons (1)
	P-element