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

DEPETRIS CHAUVIN, A; FERNÁNDEZ-GAMBA, A; GOROSTIZA EA; CASTAÑO EM ; CERIANI MF.

Big Sky, Montana

Congreso; Biannual Meeting for the Society for Research on Biological Rhythms; 2014

Society for Research on Biological Rhythms

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 through the day as synaptic contacts do as a result of a remarkable remodeling of the sLNv axonal projections. In fact these axonal projections show complex arborizations and are full of PDF-containing dense core vesicles in the early morning, whereas at the beginning of the night their complexity and PDF content are reduced. 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 (MMP 1 and 2) are key in the control of circadian structural remodeling. Adult-specific down-regulation 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 levels at the dorsal terminals and exerts a clear effect on overt behavior. In vitro analysis demonstrated that PDF is hydrolyzed by MMP1, strongly suggesting that MMP1 could terminate PDF biological activity at the dorsal terminals. These data demonstrates that MMP1 directly modulates PDF processing, which leads to daily structural remodeling and circadian behavior.