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- W2994052732 abstract "The extracellular matrix (ECM) of the myotendinous junction (MTJ) undergoes dramatic physical and biochemical remodeling during the first 48 h of development in zebrafish, transforming from a rectangular fibronectin-dominated somite boundary to a chevron-shaped laminin-dominated MTJ. Matrix metalloproteinase 11 (Mmp11, a.k.a. Stromelysin-3) is both necessary and sufficient for the removal of fibronectin at the MTJ, but whether this protease acts directly on fibronectin and how its activity is regulated remain unknown. Using immunofluorescence, we show that both paralogues of Mmp11 accumulate at the MTJ during this time period, but with Mmp11a present early and later replaced by Mmp11b. Moreover, Mmp11a also accumulates intracellularly, associated with the Z-discs of sarcomeres within skeletal muscle cells. Using the epitope-mediated MMP activation (EMMA) assay, we show that despite having a weaker paired basic amino acid motif in its propeptide than Mmp11b, Mmp11a is activated by furin, but may also be activated by other mechanisms intracellularly. One or both paralogues of tissue inhibitors of metalloproteinase-4 (Timp4) are also present at the MTJ throughout this process, and yeast two-hybrid assays reveal distinct and specific interactions between various domains of these proteins. We propose a model in which Mmp11a activity is modulated (but not inhibited) by Timp4 during early MTJ remodeling, followed by a phase in which Mmp11b activity is both inhibited and spatially constrained by Timp4 in order to maintain the structural integrity of the mature MTJ." @default.
- W2994052732 created "2019-12-13" @default.
- W2994052732 creator A5020633310 @default.
- W2994052732 creator A5063077228 @default.
- W2994052732 creator A5074138744 @default.
- W2994052732 date "2019-12-03" @default.
- W2994052732 modified "2023-10-10" @default.
- W2994052732 title "Paralogues of Mmp11 and Timp4 Interact during the Development of the Myotendinous Junction in the Zebrafish Embryo" @default.
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- W2994052732 doi "https://doi.org/10.3390/jdb7040022" @default.
- W2994052732 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6955687" @default.
- W2994052732 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31816958" @default.
- W2994052732 hasPublicationYear "2019" @default.
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