ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
p75 neurotrophin receptor mediates neuronal cell death by activating GIRK channels through phosphatidylinositol 4,5-bisphosphate.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 64 citations in OpenAlex.
- Sortilin and L-type Calcium Channels May be Involved in the Unusual Mechanism of proBDNF Signaling in Regenerating Mouse Neuromuscular Junctions.Neurochemical research · 2025Article
- Evidence that cholinergic mechanisms contribute to hyperexcitability at early stages in Alzheimer's disease.Frontiers in dementia · 2025Review
- Article
- Alzheimer's disease linked Aβ42 exerts product feedback inhibition on γ-secretase impairing downstream cell signaling.bioRxiv : the preprint server for biology · 2024Article
- Article
- Direct modulation of G protein-gated inwardly rectifying potassium (GIRK) channels.Frontiers in physiology · 2024Review
- ProBDNF and Brain-Derived Neurotrophic Factor Prodomain Differently Modulate Acetylcholine Release in Regenerating and Mature Mouse Motor Synapses.Frontiers in cellular neuroscience · 2022Article
- 2,5-Hexanedione induced apoptosis in rat spinal cord neurons and VSC4.1 cells via the proNGF/p75NTR and JNK pathways.Bioscience reports · 2021Article
- TrkA-mediated endocytosis of p75-CTF prevents cholinergic neuron death upon γ-secretase inhibition.Life science alliance · 2021Article
- Regulation of cholinergic basal forebrain development, connectivity, and function by neurotrophin receptors.Neuronal signaling · 2019Review
- Article
- G-Protein-Coupled Inwardly Rectifying Potassium (GIRK) Channel Activation by the p75 Neurotrophin Receptor Is Required for Amyloid β Toxicity.Frontiers in neuroscience · 2017Article
- Cognitive dysfunction in Huntington's disease: mechanisms and therapeutic strategies beyond BDNF.Brain pathology (Zurich, Switzerland) · 2016Review
- Converging roles of ion channels, calcium, metabolic stress, and activity pattern of Substantia nigra dopaminergic neurons in health and Parkinson's disease.Journal of neurochemistry · 2016Review
- proBDNF and p75NTR Control Excitability and Persistent Firing of Cortical Pyramidal Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Behavioral and Genetic Evidence for GIRK Channels in the CNS: Role in Physiology, Pathophysiology, and Drug Addiction.International review of neurobiology · 2015Review
- Homeostasis or channelopathy? Acquired cell type-specific ion channel changes in temporal lobe epilepsy and their antiepileptic potential.Frontiers in physiology · 2015Review
- p75 regulates Purkinje cell firing by modulating SK channel activity through Rac1.The Journal of biological chemistry · 2014Article
- Neurotrophins regulate ApoER2 proteolysis through activation of the Trk signaling pathway.BMC neuroscience · 2014Article
- Neurotrophin receptor p75 mediates the uptake of the amyloid beta (Aβ) peptide, guiding it to lysosomes for degradation in basal forebrain cholinergic neurons.Brain structure & function · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pan neurotrophin receptor p75(NTR) signals programmed cell death both during nervous system development and after neural trauma and disease in the adult. However, the molecular pathways by which death is mediated remain poorly understood. Here, we show that this cell death is initiated by activation of G-protein-coupled inwardly rectifying potassium (GIRK/Kir3) channels and a consequent potassium efflux. Death signals stimulated by neurotrophin-mediated cleavage of p75(NTR) activate GIRK channels through the generation and binding of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2/PIP2] to GIRK channels. Both GIRK channel activity and p75(NTR)-mediated neuronal death are inhibited by sequestration of PtdIns(4,5)P2 and application of GIRK channel inhibitors, whereas pertussis toxin treatment has no effect. Thus, p75(NTR) activates GIRK channels without the need for G(i/o)-proteins. Our results demonstrate a novel mode of activation of GIRK channels, representing an early step in the p75(NTR)-mediated cell death pathway and suggesting a function for these channels during nervous system development.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.