Polyubiquitination of the neurotrophin receptor p75 directs neuronal cell survival

Abstract Specific binding of nerve growth factor (NGF) to p75 neurotrophin receptor (p75 NTR ) leads to p75 NTR polyubiquitination and its subsequent interaction with TRAF6 resulting in neuronal cell survival. However, when the binding of NGF to p75 NTR was blocked with p75 antiserum, p75 NTR polyubiquitination and neuronal cell survival were impaired. Results showed that tyrosine phosphorylation of p75 NTR increased the polyubiquitination of p75 NTR and contributed to the observed apparent neuroprotective effects. Similar to p75 NTR polyubiquitination, interaction of TRAF6 with p75 NTR was NGF/tyrosine phosphorylation dependent suggesting that TRAF6 might function as an E3 ubiquitin ligase. In sum, the results show that specific binding of NGF to p75 NTR mediates neuronal cell survival.