Low-density lipoprotein receptor-related protein-1 mediates endocytic clearance of tissue inhibitor of metalloproteinases-1 and promotes its cytokine-like activities.
dc.contributor.author | Thevenard, Jessica | |
dc.contributor.author | Verzeaux, Laurie | |
dc.contributor.author | Devy, Jerôme | |
dc.contributor.author | Etique, Nicolas | |
dc.contributor.author | Jeanne, Albin | |
dc.contributor.author | Schneider, Christophe | |
dc.contributor.author | Hachet, Cathy | |
dc.contributor.author | Ferracci, Géraldine | |
dc.contributor.author | David, Marion | |
dc.contributor.author | Martiny, Laurent | |
dc.contributor.author | Charpentier, Emmanuelle | |
dc.contributor.author | Khrestchatisky, Michel | |
dc.contributor.author | Rivera, Santiago | |
dc.contributor.author | Dedieu, Stéphane | |
dc.contributor.author | Emonard, Hervé | |
dc.date.accessioned | 2015-02-12T09:06:19Z | |
dc.date.available | 2015-02-12T09:06:19Z | |
dc.date.issued | 2014 | |
dc.identifier.citation | Low-density lipoprotein receptor-related protein-1 mediates endocytic clearance of tissue inhibitor of metalloproteinases-1 and promotes its cytokine-like activities. 2014, 9 (7):e103839 PLoS ONE | en |
dc.identifier.issn | 1932-6203 | |
dc.identifier.pmid | 25075518 | |
dc.identifier.doi | 10.1371/journal.pone.0103839 | |
dc.identifier.uri | http://hdl.handle.net/10033/344383 | |
dc.description.abstract | Tissue inhibitor of metalloproteinases-1 (TIMP-1) regulates the extracellular matrix turnover by inhibiting the proteolytic activity of matrix metalloproteinases (MMPs). TIMP-1 also displays MMP-independent activities that influence the behavior of various cell types including neuronal plasticity, but the underlying molecular mechanisms remain mostly unknown. The trans-membrane receptor low-density lipoprotein receptor-related protein-1 (LRP-1) consists of a large extracellular chain with distinct ligand-binding domains that interact with numerous ligands including TIMP-2 and TIMP-3 and a short transmembrane chain with intracellular motifs that allow endocytosis and confer signaling properties to LRP-1. We addressed TIMP-1 interaction with recombinant ligand-binding domains of LRP-1 expressed by CHO cells for endocytosis study, or linked onto sensor chips for surface plasmon resonance analysis. Primary cortical neurons bound and internalized endogenous TIMP-1 through a mechanism mediated by LRP-1. This resulted in inhibition of neurite outgrowth and increased growth cone volume. Using a mutated inactive TIMP-1 variant we showed that TIMP-1 effect on neurone morphology was independent of its MMP inhibitory activity. We conclude that TIMP-1 is a new ligand of LRP-1 and we highlight a new example of its MMP-independent, cytokine-like functions. | |
dc.language.iso | en | en |
dc.title | Low-density lipoprotein receptor-related protein-1 mediates endocytic clearance of tissue inhibitor of metalloproteinases-1 and promotes its cytokine-like activities. | en |
dc.type | Article | en |
dc.contributor.department | Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. | en |
dc.identifier.journal | PloS one | en |
refterms.dateFOA | 2018-06-13T09:06:49Z | |
html.description.abstract | Tissue inhibitor of metalloproteinases-1 (TIMP-1) regulates the extracellular matrix turnover by inhibiting the proteolytic activity of matrix metalloproteinases (MMPs). TIMP-1 also displays MMP-independent activities that influence the behavior of various cell types including neuronal plasticity, but the underlying molecular mechanisms remain mostly unknown. The trans-membrane receptor low-density lipoprotein receptor-related protein-1 (LRP-1) consists of a large extracellular chain with distinct ligand-binding domains that interact with numerous ligands including TIMP-2 and TIMP-3 and a short transmembrane chain with intracellular motifs that allow endocytosis and confer signaling properties to LRP-1. We addressed TIMP-1 interaction with recombinant ligand-binding domains of LRP-1 expressed by CHO cells for endocytosis study, or linked onto sensor chips for surface plasmon resonance analysis. Primary cortical neurons bound and internalized endogenous TIMP-1 through a mechanism mediated by LRP-1. This resulted in inhibition of neurite outgrowth and increased growth cone volume. Using a mutated inactive TIMP-1 variant we showed that TIMP-1 effect on neurone morphology was independent of its MMP inhibitory activity. We conclude that TIMP-1 is a new ligand of LRP-1 and we highlight a new example of its MMP-independent, cytokine-like functions. |
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publications of the department Regulation of infection [12]
Leiter: Frau Prof. Dr. Emmanuelle Charpentier