Journal of Molecular Neuroscience

, Volume 15, Issue 3, pp 215–229

Neurotrophin dependence domain

A domain required for the mediation of apoptosis by the p75 neurotrophin receptor
  • Shahrooz Rabizadeh
  • Xin Ye
  • Sabina Sperandio
  • James J. L. Wang
  • H. Michael Ellerby
  • Lisa M. Ellerby
  • Christopher Giza
  • Rebecca L. Andrusiak
  • Harald Frankowski
  • Yifah Yaron
  • N. Nicole Moayeri
  • Giorgio Rovelli
  • Christopher J. Evans
  • Larry L. Butcher
  • Garry P. Nolan
  • Nuria Assa-Munt
  • Dale E. Bredesen
Article

DOI: 10.1385/JMN:15:3:215

Cite this article as:
Rabizadeh, S., Ye, X., Sperandio, S. et al. J Mol Neurosci (2000) 15: 215. doi:10.1385/JMN:15:3:215

Abstract

The mechanisms underlying neurotrophin dependence, and cellular dependent states in general, are unknown. We show that a 29 amino acid region in the intracellular domain of the common neurotrophin receptor, p75NTR, is required for the mediation of apoptosis by p75NTR. Furthermore, contrary to results obtained with Fas, monomeric p75NTR is required for apoptosis induction, whereas multimerization inhibits the pro-apoptotic effect. Within the 29-residue domain required for apoptosis induction by p75NTR, a 14-residue region is sufficient as a peptide inducer of apoptosis. This 14-residue peptide requires the positively charged carboxyterminal residues for its effect on cell death, and these same residues are required by the full-length p75NTR. These studies define a novel type of domain that mediates neurotrophin dependence, and suggest that other cellular dependent states may be mediated by proteins displaying similar domains.

Index Entries

p75NTRapoptosisdependenceneurotrophindimerization

Copyright information

© Humana Press Inc 2001

Authors and Affiliations

  • Shahrooz Rabizadeh
    • 1
  • Xin Ye
    • 2
  • Sabina Sperandio
    • 4
  • James J. L. Wang
    • 2
  • H. Michael Ellerby
    • 4
  • Lisa M. Ellerby
    • 4
  • Christopher Giza
    • 5
  • Rebecca L. Andrusiak
    • 2
  • Harald Frankowski
    • 4
  • Yifah Yaron
    • 8
  • N. Nicole Moayeri
    • 9
  • Giorgio Rovelli
    • 10
  • Christopher J. Evans
    • 6
  • Larry L. Butcher
    • 7
  • Garry P. Nolan
    • 11
  • Nuria Assa-Munt
    • 3
  • Dale E. Bredesen
    • 4
  1. 1.Department of GeneticsHarvard Medical SchoolBoston
  2. 2.Programs on AgingThe Burnham InstituteLa Jolla
  3. 3.Structural BiologyThe Burnham InstituteLa Jolla
  4. 4.Buck Institute for Age ResearchNovato
  5. 5.Department of NeurologyUniversity of CaliforniaLos Angeles
  6. 6.Department of PsychiatryUniversity of CaliforniaLos Angeles
  7. 7.Department of PsychologyUniversity of CaliforniaLos Angeles
  8. 8.Department of Medical Scientist Training ProgramUniversity of CaliforniaLos Angeles
  9. 9.Department of NeurosurgeryMassachusetts General HospitalBoston
  10. 10.Novartis Pharmaceuticals AGBaselSwitzerland
  11. 11.Department of Molecular Pharmacology and Microbiology and ImmunologyStanford University School of MedicineStanford