Low-density lipoprotein receptor-related protein-1 mediates endocytic clearance of tissue inhibitor of metalloproteinases-1 and promotes its cytokine-like activities.

2.50
Hdl Handle:
http://hdl.handle.net/10033/344383
Title:
Low-density lipoprotein receptor-related protein-1 mediates endocytic clearance of tissue inhibitor of metalloproteinases-1 and promotes its cytokine-like activities.
Authors:
Thevenard, Jessica; Verzeaux, Laurie; Devy, Jerôme; Etique, Nicolas; Jeanne, Albin; Schneider, Christophe; Hachet, Cathy; Ferracci, Géraldine; David, Marion; Martiny, Laurent; Charpentier, Emmanuelle; Khrestchatisky, Michel; Rivera, Santiago; Dedieu, Stéphane; Emonard, Hervé
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
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
Journal:
PloS one
Issue Date:
2014
URI:
http://hdl.handle.net/10033/344383
DOI:
10.1371/journal.pone.0103839
PubMed ID:
25075518
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
publications of the department Regulation of infection

Full metadata record

DC FieldValue Language
dc.contributor.authorThevenard, Jessicaen
dc.contributor.authorVerzeaux, Laurieen
dc.contributor.authorDevy, Jerômeen
dc.contributor.authorEtique, Nicolasen
dc.contributor.authorJeanne, Albinen
dc.contributor.authorSchneider, Christopheen
dc.contributor.authorHachet, Cathyen
dc.contributor.authorFerracci, Géraldineen
dc.contributor.authorDavid, Marionen
dc.contributor.authorMartiny, Laurenten
dc.contributor.authorCharpentier, Emmanuelleen
dc.contributor.authorKhrestchatisky, Michelen
dc.contributor.authorRivera, Santiagoen
dc.contributor.authorDedieu, Stéphaneen
dc.contributor.authorEmonard, Hervéen
dc.date.accessioned2015-02-12T09:06:19Z-
dc.date.available2015-02-12T09:06:19Z-
dc.date.issued2014-
dc.identifier.citationLow-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 ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid25075518-
dc.identifier.doi10.1371/journal.pone.0103839-
dc.identifier.urihttp://hdl.handle.net/10033/344383-
dc.description.abstractTissue 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.en
dc.language.isoenen
dc.titleLow-density lipoprotein receptor-related protein-1 mediates endocytic clearance of tissue inhibitor of metalloproteinases-1 and promotes its cytokine-like activities.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalPloS oneen

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