NGF BINDING TO P75 ENHANCES THE SENSITIVITY OF SENSORY AND SYMPATHETIC NEURONS TO NGF AT DIFFERENT STAGES OF DEVELOPMENT

To clarity the role of the common naeurotrophin receptor p75 in modula ting the survival response of sensory and sympathetic neurons to NGF a t different stages of development, we compared the actions of wild-typ e NGF with a mutated NGF protein that binds normally to TrkA, the NGF receptor tyrosine kinase, but has greatly reduced binding to p75. At s aturating concentrations, the NGF mutant promoted the survival of simi lar numbers of trigeminal sensory and sympathetic neurons as NGF. At s ubsaturating concentrations, the NGF mutant was less effective than wi ld-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, Wherea s 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 resul ts indicate that binding od NGF to p75 enhances the sensitivity of NGF -dependent neurons to NGF at stages in their development when the leve ls of p75 and TrkA are similar.