Both Drosophila matrix metalloproteinases have released and membrane-tethered forms but have different substrates

LaFever, Kimberly S.; Wang, Xiaoxi; Page-McCaw, Patrick; Bhave, Gautam; Page-McCaw, Andrea

doi:10.1038/srep44560

Cited by 38 publications

(37 citation statements)

References 55 publications

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“…Compared to challenges of testing the 24 MMPs in mammalian models, Drosophila has just 2 MMPs, secreted Mmp1 and glycosylphosphatidylinositol (GPI)-anchored Mmp2 (19–21); although one Mmp1 isoform is also GPI-anchored (22). 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).…”

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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Section: Introductionmentioning

confidence: 99%

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

2017

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“…In D. melanogaster, modulation of tissue-tissue adhesion as well as complete tissue-tissue decoupling has been previously associated with Matrix metalloprotease 1 (Mmp1) activity (Diaz-de-la-Loza et al, 2018;Glasheen et al, 2010;LaFever et al, 2017;Srivastava et al, 2007). To test whether activity of this matrix metalloprotease was involved in mechanical decoupling of serosa and yolk sac, we cloned the M. abdita orthologue of Mmp1 (Mab-Mmp1) and found it expressed in yolk sac nuclei ( Figure 5A).…”

Section: Mab-mmp1 Modulates Tissue-tissue Interaction Between Yolk Samentioning

confidence: 94%

Decoupling from yolk sac is required for extraembryonic tissue spreading in the scuttle fly Megaselia abdita

Caroti¹,

Avalos²,

Noeske³

et al. 2017

Preprint

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Evolutionary novelty can be generally traced back to continuous changes rather than disruptive transformations, yet the sudden appearance of novel developmental traits is not well understood. Here we use the extraembryonic amnioserosa in Drosophila melanogaster as example for a suddenly and newly evolved epithelium, and we ask how this tissue originated by gradual transitions from its two ancestors, amnion and serosa. To address this question, we used in toto time-lapse recordings to analyze an intermediate mode of extraembryonic development in the scuttle fly Megaselia abdita. Our results suggest that the amnioserosa evolved by loss of serosa spreading without disrupting the developmental programs of serosa and amnion. Our findings imply that the Drosophila amnioserosa has retained properties of the ancient serosa and, more generally, indicate that non-autonomous interactions between tissues can be a compelling variable for the evolution of epithelial properties. Impact StatementThe Drosophila amnioserosa originated as a composite extraembryonic epithelium by loss of epithelial spreading and rather than changes in amnion or serosa tissue differentiation.

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“…Finally, the specific targets of MMPs will be of interest to determine which ECM components are essential to prevent TMs expansion. There are two MMPs in Drosophila (MMP1 and MMP2) with 10 and 3 isoforms respectively, MMP1 and MMP2 have been classically differentiated by their extracellular or membrane associated localization, however this concept is currently under debate [15]. It is proposed that each MMP has particular targets from the ECM which are sensible of degradation, recent classifications have brought light on the specificity of each protease and the different substrates [43].…”

Section: Besides Mmps Expression Attenuation Reduces the Volume Occumentioning

confidence: 99%

“…Recent reports propose that products of both genes are found at the cell surface and released into media and that GPI-anchored MMPs promote cell adhesion when they are rendered inactive. Moreover, the two MMPs cleave different substrates, suggesting that this is the important distinction within this smallest MMP family [15].…”

Section: Introductionmentioning

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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Both Drosophila matrix metalloproteinases have released and membrane-tethered forms but have different substrates

Cited by 38 publications

References 55 publications

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

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

Decoupling from yolk sac is required for extraembryonic tissue spreading in the scuttle fly Megaselia abdita

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

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