The p75 neurotrophin receptor: effects on neuron survival in vitro and interaction with death domain-containing adaptor proteins

The p75 neurotrophin receptor (p75(NTR)) is a death domain (DD) containing receptor of the TNF/FAS(APO-1) family. p75(NTR) has recently been shown to mediate apoptosis in certain types of neurons as well as in oligodendrocyte s. The molecular mechanisms by which p75(NTR) stimulates apoptosis are stil l unknown. Here, we have tested whether overexpression of p75(NTR) could mo dulate survival of sympathetic neurons cultured in the presence or absence of NGF. Moreover, using the yeast two-hybrid system, we tested whether p75( NTR) intracellular domain was able to dimerize or interact with known DD-co ntaining proteins including FADD, RIP, RAIDD and TRADD. We found that over- expression of p75(NTR) had no effect on the survival of sympathetic neurons cultured in the presence of NGF but instead delayed neuronal death followi ng NGF deprivation. These results strongly support the finding that p75(NTR ) is not involved in the apoptosis process induced by NGF deprivation in sy mpathetic neurons. We also found that the intracellular domain of p75(NTR) failed to associate either with itself or with other known DD-containing pr oteins. This suggests that the mechanisms by which p75(NTR) triggers apopto sis in certain cell types are different from those used by other receptors of the TNF/FAS family.