ProBDNF Induces Neuronal Apoptosis via Activation of a Receptor Complex of p75NTRand Sortilin

• DOI: 10.1523/jneurosci.5123-04.2005
• Publication Date: 2005-06-01T20:33:22Z
• Authors: Henry K. Teng; Kenneth K. Teng; Ramee Lee; Saundrene Wright; Seema Tevar; Ramiro D. Almeida; Pouneh Kermani; Risa Torkin; Zhe-Yu Chen; Francis S. Lee; Rosemary T. Kraemer; Anders Nykjaer; Barbara L. Hempstead
• Keywords: Mice, Knockout; Neurons; 0303 health sciences; Membrane Glycoproteins; Brain-Derived Neurotrophic Factor; Brain; Apoptosis; Nerve Tissue Proteins; Ligands; Receptor, Nerve Growth Factor; Cell Line; Rats; Rats, Sprague-Dawley; Adaptor Proteins, Vesicular Transport; Mice; 03 medical and health sciences; Animals; Humans; Receptor, trkB; Receptors, Growth Factor; Phosphorylation; Protein Precursors

Brain-derived neurotrophic factor (BDNF) is best characterized for critical roles in neuronal survival, differentiation, and synaptic modulation mediated by the TrkB receptor tyrosine kinase. Developmentally regulated death signaling BDNF has also been demonstrated via activation of p75 NTR . Because recent studies suggest that proNGF, precursor form NGF, more active than mature NGF inducing apoptosis after binding to a coreceptor, sortilin, we asked whether (proBDNF) proapoptotic ligand nervous system. proBDNF secreted cultured neurons, recombinant binds sortilin. In sympathetic neurons coexpressing sortilin , found an apoptotic induces at subnanomolar concentrations. contrast, BDNF, but not proBDNF, effective phosphorylation. effects are dependent on cellular coexpression both because deficient resistant proBDNF-induced apoptosis, competitive antagonists block neuron death. Moreover, addition preformed complexes soluble failed induce cells suggesting interaction with receptors cell surface required initiate Together our past findings, these data neurotrophin family capable modulating diverse biological processes differential processing proneurotrophins.