Abstract
Author SummaryIn the fruit fly Drosophila melanogaster, the neuropeptide Pigment Dispersing Factor (PDF) supports circadian function by synchronizing two types of pacemaker cells, M cells and E cells. The PDF receptor (PDF-R) is a G protein coupled receptor (GPCR) whose activation stimulates adenylate cyclase (AC), thereby elevating levels of the second messenger cAMP in many different pacemakers including M cells. Drosophila contains at least 12 genes that encode potential ACs. In this study, we identify the AC downstream of the PDF receptor specifically in M cells and show that PDF signals preferentially through AC3. However, other GPCRs in the very same cells do not rely on AC3. A different scaffolding protein also influences PDF responses in M cells, suggesting that signaling components are spatially grouped to allow for coupling of specific receptors with downstream components. Remarkably, in E pacemakers, AC3 disruptions have no effect. These findings suggest that distinct PDF circadian signals exist in M versus in E pacemakers, and more generally, we propose a mechanism to differentiate signaling pathways that use common components.
Highlights
The importance of biological rhythms in the anticipation and response to daily environmental changes is underscored by their conservation throughout nature
In E pacemakers, AC3 disruptions have no effect. These findings suggest that distinct Pigment Dispersing Factor (PDF) circadian signals exist in M versus in E pacemakers, and more generally, we propose a mechanism to differentiate signaling pathways that use common components
The present study asks: What is the identity of downstream components that are associated with PDF receptor (PDF-R) signaling pathways in different circadian pacemaker neurons? using live imaging of intact fly brains, we identify the particular adenylate cyclase (AC) isoform that is associated with PDF signaling in small ventro-lateral neuron (LNv)—commonly called M cells
Summary
The importance of biological rhythms in the anticipation and response to daily environmental changes is underscored by their conservation throughout nature In eukaryotes, these rhythms are generated by a set of core clock genes that contrive to produce interlocked feedback loops. Previous work indicates that these subgroups are functionally as well as anatomically distinct and that certain cells are associated with specific components of daily locomotor behavior These associations are subject to specific environmental conditions, and they display considerable plasticity under different light and temperature conditions [2,3,5,6,7,8]. Neuropeptides are critical mediators of intercellular communication between pacemaker cells in both mammals and Drosophila and a number are expressed in the Drosophila clock cell system, including the Pigment Dispersing Factor (PDF) [11,12,13,14]
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