Neurotrophin dependence domain - A domain required for the mediation of apoptosis by the p75 neurotrophin receptor

The mechanisms underlying neurotrophin dependence, and cellular dependent s tates in general, are unknown. We show that a 29 amino acid region in the i ntracellular domain of the common neurotrophin receptor, p75(NTR), is requi red for the mediation of apoptosis by p75(NTR) Furthermore, contrary to res ults obtained with Fas, monomeric p75(NTR) is required for apoptosis induct ion, whereas multimerization inhibits the pro-apoptotic effect. Within the 29-residue domain required for apoptosis induction by p75(NTR), a 14-residu e region is sufficient as a peptide inducer of apoptosis. This 14-residue p eptide requires the positively charged carboxyterminal residues for its eff ect on cell death, and these same residues are required by the full-length p75(NTR). These studies define a novel type of domain that mediates neurotr ophin dependence, and suggest that other cellular dependent states may be m ediated by proteins displaying similar domains.