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The low‐affinity nerve growth factor receptor p75 NGFR mediates death of PC12 cells after nerve growth factor withdrawal
Author(s) -
Barrett G.L.,
Georgiou A.
Publication year - 1996
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19960715)45:2<117::aid-jnr4>3.0.co;2-d
Subject(s) - nerve growth factor , cell sorting , low affinity nerve growth factor receptor , receptor , programmed cell death , biology , transfection , medicine , microbiology and biotechnology , endocrinology , cell , cell culture , apoptosis , biochemistry , genetics
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 down‐regulate 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. © 1996 Wiley‐Liss, Inc.