NGF binding to p75 enhances the sensitivity of sensory and sympathetic neurons to NGF at different stages of development.
To clarify the role of the common neurotrophin receptor p75 in modulating the survival response of sensory and sympathetic neurons to NGF at different stages of development, we compared the actions of wild-type NGF with a mutated NGF protein that binds normally to TrkA, the NGF receptor tyrosine kinase, but has greatly reduced binding to p75. At saturating concentrations, the NGF mutant promoted the survival of similar numbers of trigeminal sensory and sympathetic neurons as NGF. At subsaturating concentrations, the NGF mutant was less effective than wild-type NGF in promoting the survival of embryonic sensory neurons and postnatal sympathetic neurons but was equally effective as wild-type NGF in promoting the survival of embryonic sympathetic neurons. Whereas the levels of trkA and p75 were similar in embryonic sensory neurons and postnatal sympathetic neurons, the level of p75 was significantly lower than that of trkA in embryonic sympathetic neurons. These results indicate that binding of NGF to p75 enhances the sensitivity of NGF-dependent neurons to NGF at stages in their development when the levels of p75 and TrkA are similar.
Horton
A
A
School of Biological and Medical Sciences, University of St. Andrews, Fife, Scotland, United Kingdom.
Laramee
G
G
Wyatt
S
S
Shih
A
A
Winslow
J
J
Davies
A M
AM
D000818:Animals; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D002642:Chick Embryo; D004622:Embryo, Mammalian; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA