Mmp1 processing of the PDF neuropeptide regulates circadian structural plasticity of pacemaker neurons.

Ana Depetris-Chauvin,E Axel Gorostiza,M Fernanda Ceriani,Anastasia Herrero,Eduardo M Castaño,Ágata Fernández-Gamba,Paul H Taghert

doi:10.1371/journal.pgen.1004700

Ana Depetris-Chauvin, E Axel Gorostiza + Show 5 more

Open Access

https://doi.org/10.1371/journal.pgen.1004700

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Abstract

In the Drosophila brain, the neuropeptide PIGMENT DISPERSING FACTOR (PDF) is expressed in the small and large Lateral ventral neurons (LNvs) and regulates circadian locomotor behavior. Interestingly, PDF immunoreactivity at the dorsal terminals changes across the day as synaptic contacts do as a result of a remarkable remodeling of sLNv projections. Despite the relevance of this phenomenon to circuit plasticity and behavior, the underlying mechanisms remain poorly understood. In this work we provide evidence that PDF along with matrix metalloproteinases (Mmp1 and 2) are key in the control of circadian structural remodeling. Adult-specific downregulation of PDF levels per se hampers circadian axonal remodeling, as it does altering Mmp1 or Mmp2 levels within PDF neurons post-developmentally. However, only Mmp1 affects PDF immunoreactivity at the dorsal terminals and exerts a clear effect on overt behavior. In vitro analysis demonstrated that PDF is hydrolyzed by Mmp1, thereby suggesting that Mmp1 could directly terminate its biological activity. These data demonstrate that Mmp1 modulates PDF processing, which leads to daily structural remodeling and circadian behavior.

Highlights

The rotation of the earth around its own axis imposes cyclic changes on environmental conditions, primarily through variations on luminosity and temperature
Downregulation of EcR affected PIGMENT DISPERSING FACTOR (PDF) neurons per se, clamping the structure in the more complex, highly arborized, configuration (Figure S3 B and [33]). Together these results demonstrate that the daily axonal remodeling of PDF neurons is a complex and highly regulated process that depends on the concerted activity of matrix metalloproteinases (Mmps), Fasciclin 2 and the Ecdysone Receptor
We studied the molecular mechanisms responsible for the axonal remodeling of sLNvs terminals, a unique type of structural plasticity that comprises spatial long scale changes on a daily basis

Summary

Introduction

The rotation of the earth around its own axis imposes cyclic changes on environmental conditions, primarily through variations on luminosity and temperature. We have demonstrated that the sLNvs axonal terminals exhibit a higher degree of complexity during the day and a reduced complexity during the night accompanying the daily changes in PDF levels [14]. This circadian structural plasticity may result in a change in synaptic partners at different times of the day and might offer another relevant mechanism to transmit time of day information [15]

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