Bruce Douglas Carter

Learn More
Members of the nerve growth factor (NGF) family promote the survival of neurons during development. NGF specifically activates the receptor trkA, initiating a signal transduction cascade which ultimately blocks cell death. Here we show that NGF can have the opposite effect, inducing the death of mature oligodendrocytes cultured from postnatal rat cerebral(More)
Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) selectively bind to distinct members of the Trk family of tyrosine kinase receptors, but all three bind with similar affinities to the neurotrophin receptor p75 (p75NTR). The biological significance of neurotrophin binding to p75NTR in cells that also express Trk(More)
In addition to its role as a survival factor, nerve growth factor (NGF) has been implicated in initiating apoptosis in restricted cell types both during development and after terminal cell differentiation. NGF binds to the TrkA tyrosine kinase and the p75 neurotrophin receptor, a member of the tumor necrosis factor cytokine family. To understand the(More)
The tyrosine kinase receptor trkB is thought to mediate the biological actions of brain-derived neurotrophic factor. This receptor is expressed by a large variety of neurons during development. Truncated trkB molecules lacking the tyrosine kinase domain have also been described, but their functions remain elusive. In order to gain insight into their role,(More)
Germline NF1, c-RET, SDH, and VHL mutations cause familial pheochromocytoma. Pheochromocytomas derive from sympathetic neuronal precursor cells. Many of these cells undergo c-Jun-dependent apoptosis during normal development as NGF becomes limiting. NF1 encodes a GAP for the NGF receptor TrkA, and NF1 mutations promote survival after NGF withdrawal. We(More)
NRIF (neurotrophin receptor interacting factor) is a ubiquitously expressed zinc finger protein of the Krüppel family which interacts with the neurotrophin receptor p75(NTR). The interaction was first detected in yeast and then biochemically confirmed using recombinant GST-NRIF fusions and p75(NTR) expressed by eukaryotic cells. Transgenic mice carrying a(More)
The p75 neurotrophin receptor regulates neuronal survival, promoting it in some contexts yet activating apoptosis in others. The mechanism by which the receptor elicits these differential effects is poorly understood. Here, we demonstrate that p75 is cleaved by gamma-secretase in sympathetic neurons, specifically in response to proapoptotic ligands. This(More)
Peripheral myelin formation is initiated by axonal cues that trigger a differentiation program in associated Schwann cells. Here, we define one essential differentiation signal: activation of the transcription factor NF-κB. In rat sciatic nerves, NF-κB was highly upregulated in pre-myelinating Schwann cells, and then its expression progressively declined(More)
Ligand-mediated dimerization has emerged as a universal mechanism of growth factor receptor activation. Neurotrophins interact with dimers of the p75 neurotrophin receptor (p75(NTR)), but the mechanism of receptor activation has remained elusive. Here, we show that p75(NTR) forms disulphide-linked dimers independently of neurotrophin binding through the(More)
VHL, NF-1, c-Ret, and Succinate Dehydrogenase Subunits B and D act on a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells and requires the EglN3 prolyl hydroxylase as a downstream effector. Germline mutations of these genes cause familial pheochromocytoma and other neural(More)