Blocking nerve growth factor binding to the p75 neurotrophin receptor on sympathetic neurons transiently reduces trkA activation but does not affect neuronal survival.
Nerve growth factor interacts with the trkA tyrosine kinase receptor and with the p75 neurotrophin receptor. It is clear that trkA mediates most, if not all, of the stereotypical responses of sympathetic neurons to nerve growth factor but the role of the p75 neurotrophin receptor is unclear. In this study, we have asked whether a functional interaction between p75 neurotrophin receptor and trkA exists in primary sympathetic neurons by disrupting nerve growth factor binding to p75 neurotrophin receptor. Acute assays reveal that blocking antibodies directed against p75 neurotrophin receptor reduce nerve growth factor-mediated trkA tyrosine phosphorylation and reduce the amount of nerve growth factor which binds the trkA receptor. This reduction in trkA activity is relatively short-lived in vitro and blocking antibodies to p75 neurotrophin receptor do not inhibit long-term survival of nerve growth factor-dependent primary neurons. Together, these data indicate that p75 neurotrophin receptor and trkA interact within primary neurons to enhance nerve growth factor binding to the trkA receptor under conditions of acute but not chronic nerve growth factor exposure.
Lachance
C
C
Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Quebec, Canada.
Belliveau
D J
DJ
Barker
P A
PA
D000818:Animals; D002470:Cell Survival; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D014443:Tyrosine