The role of the p75 neurotrophin receptor (p75(NTR)) in adult cholinergic basal forebrain (cBF) neurons is unclear due to conflicting results from previous studies and to limitations of existing p75(NTR)-knock-out mouse models. In the present study we used a novel conditional knock-out line (ChAT-cre p75(in/in)) to assess the role of p75(NTR) in the cBF by eliminating p75(NTR) in choline acetyl...

The generation of biologically active proteins by regulated intramembrane proteolysis is a highly conserved mechanism in cell signaling. Presenilin-dependent gamma-secretase activity is responsible for the intramembrane proteolysis of selected type I membrane proteins, including beta-amyloid precursor protein (APP) and Notch. A small fraction of intracellular domains derived from both APP and N...

PC12-27, a PC12 clone characterized by high levels of the transcription repressor REST and by very low mTORC2 activity, had been shown to be unresponsive to NGF, possibly because of its lack of the specific TrkA receptor. The neurotrophin receptor repressed by high REST in PC12-27 cells, however, is shown now to be not TrkA, which is normal, but p75, whose expression is inhibited at the transcr...

Hypothalamic neurons control a variety of important hormonal and behavioral functions. Little is known, however, about the neurotrophic factors that these neurons may require for survival and/or maintenance of their differentiated functions. We conducted experiments to examine this issue, utilizing a combination of immunohistochemical, in situ hybridization and cell culture approaches. We found...

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 deletion in the exon encoding the p75(N...

The p75 neurotrophin receptor has been implicated in multiple biological and pathological processes. While significant advances have recently been made in understanding the physiologic role of p75, many details and aspects remain to be determined. This is in part because the two existing knockout mouse models (Exons 3 or 4 deleted, respectively), both display features that defy definitive concl...

During development many of neurons die by the phenomenon named programmed cell death or apoptosis and this reaction is regulated by neurotrophin (BDNF, NGF, NT3 and NT4/5). These neurotrophins bind to two different classes of transmembrane receptor proteins, the Trks and P75 NTR. Axotomy can induce apoptosis after birth and deprenyl is a an inhibitor of monoamineoxidase type-B and seems to act ...

We have identified a new function for the dynein adaptor Bicaudal D homolog 1 (BICD1) by screening a siRNA library for genes affecting the dynamics of neurotrophin receptor-containing endosomes in motor neurons (MNs). Depleting BICD1 increased the intracellular accumulation of brain-derived neurotrophic factor (BDNF)-activated TrkB and p75 neurotrophin receptor (p75(NTR)) by disrupting the endo...

Neurotrophins mediate their effects by binding to members of the Trk family of receptor tyrosine kinases and the neurotrophin receptor p75 [1]. Whereas Trks are essential for the trophic effects of neurotrophins [1], p75 has distinct functions in different cells. For example, it enhances the survival response of certain neurons to nerve growth factor (NGF) [2], but mediates a cytotoxic response...

TRAF6 is an E3 ubiquitin ligase that mediates signaling from members of the tumor necrosis factor and Toll-like receptor superfamilies, including the p75 neurotrophin receptor. Recently, TRAF6 was shown to bind to another p75 cytoplasmic interactor, NRIF, and promote its nuclear localization. Here, we demonstrate that NRIF is a substrate for TRAF6-mediated K63 polyubiquitination and that this m...