Low-density lipoprotein receptor-related protein-1 mediates endocytic clearance of tissue inhibitor of metalloproteinases-1 and promotes its cytokine-like activities.
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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.
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 ONE
AffiliationHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
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- Low density lipoprotein receptor-related protein mediates endocytic clearance of pro-MMP-2.TIMP-2 complex through a thrombospondin-independent mechanism.
- Authors: Emonard H, Bellon G, Troeberg L, Berton A, Robinet A, Henriet P, Marbaix E, Kirkegaard K, Patthy L, Eeckhout Y, Nagase H, Hornebeck W, Courtoy PJ
- Issue date: 2004 Dec 24
- Intrinsic dynamics study identifies two amino acids of TIMP-1 critical for its LRP-1-mediated endocytosis in neurons.
- Authors: Verzeaux L, Belloy N, Thevenard-Devy J, Devy J, Ferracci G, Martiny L, Dedieu S, Dauchez M, Emonard H, Etique N, Devarenne-Charpentier E
- Issue date: 2017 Jul 14
- Dissecting the interaction between tissue inhibitor of metalloproteinases-3 (TIMP-3) and low density lipoprotein receptor-related protein-1 (LRP-1): Development of a "TRAP" to increase levels of TIMP-3 in the tissue.
- Authors: Scilabra SD, Yamamoto K, Pigoni M, Sakamoto K, Müller SA, Papadopoulou A, Lichtenthaler SF, Troeberg L, Nagase H, Kadomatsu K
- Issue date: 2017 May
- A new role for TIMP-1 in modulating neurite outgrowth and morphology of cortical neurons.
- Authors: Ould-yahoui A, Tremblay E, Sbai O, Ferhat L, Bernard A, Charrat E, Gueye Y, Lim NH, Brew K, Risso JJ, Dive V, Khrestchatisky M, Rivera S
- Issue date: 2009 Dec 14
- Differential regulation of extracellular tissue inhibitor of metalloproteinases-3 levels by cell membrane-bound and shed low density lipoprotein receptor-related protein 1.
- Authors: Scilabra SD, Troeberg L, Yamamoto K, Emonard H, Thøgersen I, Enghild JJ, Strickland DK, Nagase H
- Issue date: 2013 Jan 4