Mmp1 Processing of the PDF Neuropeptide Regulates Circadian Structural Plasticity of Pacemaker Neurons

Depetris-Chauvin, Ana; Fernandez-Gamba, A.; Gorostiza, Ezequiel Axel; Herrero, Anastasia; Castaño, Eduardo M.; Ceriani, M. Fernanda

doi:10.1371/journal.pgen.1004700

Cited by 44 publications

(57 citation statements)

References 70 publications

(106 reference statements)

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“…When the Pdf + LNvs are acutely silenced, the s‐LNv projections have reduced axonal complexity throughout the day (Depetris‐Chauvin et al., ) and the flies display arrhythmic rest:activity behavior, although the s‐LNv molecular clock still runs with a normal 24‐hr period, suggesting that electrical activity is an output of the molecular clock and regulates remodeling of s‐LNv projections. The circadian remodeling of s‐LNv projections is also regulated by cell‐autonomous expression of PDF and Mmp1, a matrix metalloproteinase that processes PDF (Depetris‐Chauvin et al., ).…”

Section: Circadian Regulation Of Structural Plasticity In S‐lnvsmentioning

confidence: 99%

Molecular and circuit mechanisms mediating circadian clock output in the Drosophila brain

King

Sehgal

2018

Eur J of Neuroscience

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A central question in the circadian biology field concerns the mechanisms that translate ~24-hr oscillations of the molecular clock into overt rhythms. Drosophila melanogaster is a powerful system that provided the first understanding of how molecular clocks are generated and is now illuminating the neural basis of circadian behavior. The identity of ~150 clock neurons in the Drosophila brain and their roles in shaping circadian rhythms of locomotor activity have been described before. This review summarizes mechanisms that transmit time-of-day signals from the clock, within the clock network as well as downstream of it. We also discuss the identification of functional multisynaptic circuits between clock neurons and output neurons that regulate locomotor activity.

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Section: Circadian Regulation Of Structural Plasticity In S‐lnvsmentioning

confidence: 99%

Molecular and circuit mechanisms mediating circadian clock output in the Drosophila brain

King

Sehgal

2018

Eur J of Neuroscience

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“…Both Mmps regulate motor neuron axon defasciculation, with the matrix molecule Faulty Attraction (Frac) identified as an Mmp2 substrate promoting motor axon targeting (23, 24). Both Mmps also regulate synaptogenesis in multiple contexts, including reshaping dendritic arbors (25, 26) and axonal terminals (27). At the NMJ, these two Mmps coordinate structural and functional synaptogenesis by heparan sulfate proteoglycan (HSPG)-dependent regulation of Wnt Wingless (Wg) trans -synaptic signaling (7).…”

Section: Introductionmentioning

confidence: 99%

Neuronal activity drives FMRP- and HSPG-dependent matrix metalloproteinase function required for rapid synaptogenesis

2017

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Matrix metalloproteinase (MMP) functions modulate synapse formation and activity-dependent plasticity, with MMP dysfunction implicated in Fragile X syndrome (FXS), a disease caused by the loss of the RNA binding protein FMRP and characterized by neurological dysfunction and intellectual disability. Gene expression studies in Drosophila suggest that Mmps cooperate with the heparan sulfate proteoglycan (HSPG) glypican co-receptor Dally-like protein (Dlp) to restrict trans-synaptic Wnt signaling, and that synaptogenic defects in the fly model of FXS are alleviated by both Mmp inhibition and Dlp genetic reduction. Here, we used the Drosophila neuromuscular junction (NMJ) glutamatergic synapse to test activity-dependent Dlp and Mmp intersections in the context of FXS. We found that rapid, activity-dependent synaptic bouton formation was dependent upon secreted Mmp1. Acute neuronal stimulation reduced Mmp2 abundance, but increased that of both Mmp1 and Dlp as well as Dlp and Mmp1 co-localization at the synapse. Dlp function bidirectionally controlled Mmp1 abundance, localization and proteolytic activity around synapses. Dlp glycosaminoglycan (GAG) chains mediated this functional interaction with Mmp1. In the FXS fly model, activity-dependent increases in Mmp1 abundance and activity were lost but were restored by reducing the amount of synaptic Dlp. These data indicate that neuronal activity-induced, HSPG-dependent Mmp regulation drives activity-dependent synaptogenesis, and that this is impaired in FXS. Thus exploring this mechanism further may reveal therapeutic targets with potential to restore synaptogenesis in FXS patients.

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“…To determine the contribution of MMPs to Fz1 receptor accumulation and Wg vampirization [13] we carried out functional studies. But first, UAS-MMP1 and UAS-MMP2 RNAi tools [54] were validated in epithelial tissues ( Figure S6). MMP1 or MMP2…”

Section: Tms Expansion Requires Mmpsmentioning

confidence: 99%

Wingless promotes JNK/MMPs positive feedback loop mediate tumour microtubes expansion, glioma progression and neurodegeneration

Portela

Fahey-Lozano

2019

Preprint

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Glial cells display a network of projections (cytonemes) which mediate cell to cell communication. Under pathological conditions like glioblastoma (GB), cytonemes transform into ultra-long tumour microtubes (TMs). These filopodia infiltrate through the brain, enwrap neurons and deplete wingless (Wg)/WNT, as a consequence GB progress and neurons undergo synapse loss and degeneration. Thus TMs emerge as a central cellular feature of GB which correlates with a poor prognosis in patients and animal models. Here we describe in a Drosophila model for GB the molecular mechanisms behind TMs production, infiltration and maintenance. Glial cells are initially transformed into malignant GB upon EGFR and PI3K pathways constitutive activation, afterwards GB cells establish a positive feedback loop including Wg signalling, JNK and matrix metalloproteases (MMP). In order, Frizzled1 mediates Wg signalling upregulation which activates JNK in GB. As a consequence, MMPs are upregulated and facilitate TMs infiltration in the brain, hence GB TMs network expands and mediate further wingless depletion to close the loop.

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Mmp1 Processing of the PDF Neuropeptide Regulates Circadian Structural Plasticity of Pacemaker Neurons

Cited by 44 publications

References 70 publications

Molecular and circuit mechanisms mediating circadian clock output in the Drosophila brain

Molecular and circuit mechanisms mediating circadian clock output in the Drosophila brain

Neuronal activity drives FMRP- and HSPG-dependent matrix metalloproteinase function required for rapid synaptogenesis

Wingless promotes JNK/MMPs positive feedback loop mediate tumour microtubes expansion, glioma progression and neurodegeneration

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