The neurotrophin receptor p75 binds neurotrophin-3 on sympathetic neurons with high affinity and specificity.

High-affinity neurotrophin-3 (NT3) receptors have been identified on nerve growth factor (NGF)-dependent sympathetic neurons, but their occupancy by NT3 does not lead to neuronal survival. The molecular nature of these NT3 binding sites was investigated in this study. With freshly dissociated embryonic day 11 (E11) chick sympathetic neurons, cross-linking experiments revealed that the main receptor responsible for high-affinity specific binding was the neurotrophin receptor p75 (p75(NTR)), with only a small fraction corresponding to trkC. When E11 sympathetic neurons were cultured in the presence of NGF, trkC transcripts became undetectable, but high-affinity specific NT3 binding persisted. Cross-linking and antibody inhibition experiments indicated that p75(NTR) was the only detectable NT3 receptor protein. These characteristics were not observed when p75(NTR) was expressed in transformed cells. We conclude that p75(NTR) can exist in neurons in a confirmation conferring hitherto unrecognized properties to this receptor.