The low-affinity nerve growth factor receptor p75(NGFR) mediates death of PC12 cells after nerve growth factor withdrawal
- Author(s)
- Barrett, GL; Georgiou, A;
- Details
- Publication Year 1996-07-15,Volume 45,Issue #2,Page 117-128
- Journal Title
- JOURNAL OF NEUROSCIENCE RESEARCH
- Publication Type
- Journal Article
- Abstract
- We have investigated the role of the low-affinity nerve growth factor (NGF) receptor p75(NGFR) in determining the death of neuronally differentiated PC12 cells after withdrawal of NGF. A range of high and low p75(NGFR)-expressing cells were obtained by a combination of fluorescence activated cell sorting (FACS) and stable transfection with a p75(NGFR) expression vector. Cells were readily differentiated to a neuronal phenotype irrespective of the level of p75(NGFR) expression. However, the rate and extent of neuronal death following NGF deprivation were extremely sensitive to the level of p75(NGFR) expression. The highest expressing cells died most rapidly. Cells selected for very low levels of p75(NGFR) expression exhibited resistance to NGF withdrawal, and remained as viable, differentiated neurons, with minimal cell death, for at least 5 days in the absence of NGF. Antisense oligonucleotides against p75(NGFR) were shown to downregulate p75(NGFR) in PC12 cells and, further, to significantly enhance survival in the absence of NGF. These results consolidate and generalize our previous findings that p75(NGFR) induces cell death in postnatal sensory neurons in the absence of NGF. The ability to induce cell death in the absence of NGF appears to be a more general role of p75(NGFR) in differentiated neurons, and an important new paradigm for the mechanism of NGF-dependent survival. (C) 1996 Wiley-Liss, Inc.
- Publisher
- WILEY-LISS
- Keywords
- PRIMARY SENSORY NEURONS; NGF RECEPTOR; SIGNAL-TRANSDUCTION; TRK; EXPRESSION; BINDING; DIFFERENTIATION; PROTOONCOGENE; SYSTEM; RESPONSES
- Publisher's Version
- https://doi.org/10.1002/(SICI)1097-4547(19960715)45:2<117::AID-JNR4>3.0.CO;2-D
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- Refer to copyright notice on published article.
Creation Date: 1996-07-15 12:00:00