Sortilin is essential for proNGF-induced neuronal cell death

被引:0
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作者
Anders Nykjaer
Ramee Lee
Kenneth K. Teng
Pernille Jansen
Peder Madsen
Morten S. Nielsen
Christian Jacobsen
Marco Kliemannel
Elisabeth Schwarz
Thomas E. Willnow
Barbara L. Hempstead
Claus M. Petersen
机构
[1] Aarhus University,Department of Medical Biochemistry, Ole Worms Allé 170
[2] ReceptIcon Aps,Institute for Biotechnology
[3] Weill Medical College of Cornell University,undefined
[4] Max-Delbrück-Center for Molecular Medicine,undefined
[5] Martin-Luther-Universität,undefined
来源
Nature | 2004年 / 427卷
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摘要
Sortilin1 (∼95 kDa) is a member of the recently discovered family of Vps10p-domain receptors2,3, and is expressed in a variety of tissues, notably brain, spinal cord and muscle. It acts as a receptor for neurotensin4,5, but predominates in regions of the nervous system that neither synthesize nor respond to this neuropeptide6, suggesting that sortilin has additional roles. Sortilin is expressed during embryogenesis7 in areas where nerve growth factor (NGF) and its precursor, proNGF, have well-characterized effects6,7. These neurotrophins can be released by neuronal tissues8,9, 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 TrkA11. 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.
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页码:843 / 848
页数:5
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