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Sortilin is essential for proNGF-induced neuronal cell death

Item Type:Article
Title:Sortilin is essential for proNGF-induced neuronal cell death
Creators Name:Nykjaer, A. and Lee, R. and Teng, K.K. and Jansen, P. and Madsen, P. and Nielsen, M.S. and Jacobsen, C. and Kliemannel, M. and Schwarz, E. and Willnow, T.E. and Hempstead, B.L. and Petersen, C.M.
Abstract:Sortilin (approximately 95 kDa) is a member of the recently discovered family of Vps10p-domain receptors, and is expressed in a variety of tissues, notably brain, spinal cord and muscle. It acts as a receptor for neurotensin, but predominates in regions of the nervous system that neither synthesize nor respond to this neuropeptide, suggesting that sortilin has additional roles. Sortilin is expressed during embryogenesis in areas where nerve growth factor (NGF) and its precursor, proNGF, have well-characterized effects. These neurotrophins can be released by neuronal tissues, and they regulate neuronal development through cell survival and cell death signalling. NGF regulates cell survival and cell death via binding to two different receptors, TrkA and p75NTR (ref. 10). In contrast, proNGF selectively induces apoptosis through p75NTR but not TrkA. However, not all p75NTR-expressing cells respond to proNGF, suggesting that additional membrane proteins are required for the induction of cell death. Here we report that proNGF creates a signalling complex by simultaneously binding to p75NTR and sortilin. Thus sortilin acts as a co-receptor and molecular switch governing the p75NTR-mediated pro-apoptotic signal induced by proNGF.
Keywords:Vesicular Transport Adaptor Proteins, Apoptosis, Carrier Proteins, Cell Line, Cell Membrane, Electron Spin Resonance Spectroscopy, Ligands, Macromolecular Substances, Membrane Glycoproteins, Membrane Proteins, Molecular Weight, Nerve Growth Factor, Nerve Tissue Proteins, Neurons, Protein Binding, Protein Precursors, Tertiary Protein Structure, Nerve Growth Factor Receptor, trkA Receptor, Nerve Growth Factor Receptors, Animals, Mice
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:427
Number:6977
Page Range:843-848
Date:26 February 2004
Official Publication:https://doi.org/10.1038/nature02319
PubMed:View item in PubMed

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