Dimerization-dependent block of the proapoptotic effect of p75(NTR)

The biochemical mechanism by which neurons become dependent on neurotrophin s for survival is unknown. We found previously that the common neurotrophin receptor, p75(NTR), is a mediator of neurotrophin dependence and that this effect requires a novel type of domain dubbed a neurotrophin dependence do main. We report here that, in contrast to other proapoptotic receptors such as Fas, apoptosis induction by p75(NTR) requires monomerization, with dime rization inhibiting the effect. Blocking the proapoptotic effect of the mon omer by dimerization requires a distinct domain that lies at the carboxyter minus of p75(NTR) These results define a novel type of domain required for inhibiting apoptosis induction by p75(NTR). (C) 2000 Wiley-Liss, Inc.