ArticleCell reports2016
The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
- Exploring roles of neuroglobin in oxygen homeostasis and neurodevelopment based on human cerebral organoid models.iScience · 2026Article
- Filamin A in focus: unravelling the multifaceted roles of filamin A in neurodevelopment and neurological disorders.Brain : a journal of neurology · 2025Review
- Reducing Filamin A Restores Cortical Synaptic Connectivity and Early Social Communication Following Cellular Mosaicism in Autism Spectrum Disorder Pathways.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Charting the importance of filamin A posttranslational modifications.The Biochemical journal · 2024Review
- Recent Advances and Therapeutic Implications of 2-Oxoglutarate-Dependent Dioxygenases in Ischemic Stroke.Molecular neurobiology · 2024Review
- Oxygen-regulated post-translation modifications as master signalling pathway in cells.EMBO reports · 2023Review
- Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress.Neuroprotection (Chichester, England) · 2023Article
- ULK phosphorylation of STX17 controls autophagosome maturation via FLNA.The Journal of cell biology · 2023Article
- Review
- E4BP4 Coordinates Circadian Control of Cognition in Delirium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Neurovascular responses to neuronal activity during sensory development.Frontiers in cellular neuroscience · 2022Article
- Clinical Potential of Hypoxia Inducible Factors Prolyl Hydroxylase Inhibitors in Treating Nonanemic Diseases.Frontiers in pharmacology · 2022Review
- Cirbp-PSD95 axis protects against hypobaric hypoxia-induced aberrant morphology of hippocampal dendritic spines and cognitive deficits.Molecular brain · 2021Article
- A CRHR1 antagonist prevents synaptic loss and memory deficits in a trauma-induced delirium-like syndrome.Molecular psychiatry · 2021Article
- Von Hippel-Lindau tumor suppressor pathways & corresponding therapeutics in kidney cancer.Journal of genetics and genomics = Yi chuan xue bao · 2021Review
- Ultrastructural comparison of dendritic spine morphology preserved with cryo and chemical fixation.eLife · 2020Article
- Understanding the Oxygen-Sensing Pathway and Its Therapeutic Implications in Diseases.The American journal of pathology · 2020Review
- Effect of acute pentylenetetrazol injection induced epileptic seizures on rat dentate gyrus at different postnatal ages.Anatomy & cell biology · 2020Article
- The neuronal oxygen-sensing pathway controls postnatal vascularization of the murine brain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Lack of activity of recombinant HIF prolyl hydroxylases (PHDs) on reported non-HIF substrates.eLife · 2019Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal function is highly sensitive to changes in oxygen levels, but how hypoxia affects dendritic spine formation and synaptogenesis is unknown. Here we report that hypoxia, chemical inhibition of the oxygen-sensing prolyl hydroxylase domain proteins (PHDs), and silencing of Phd2 induce immature filopodium-like dendritic protrusions, promote spine regression, reduce synaptic density, and decrease the frequency of spontaneous action potentials independently of HIF signaling. We identified the actin cross-linker filamin A (FLNA) as a target of PHD2 mediating these effects. In normoxia, PHD2 hydroxylates the proline residues P2309 and P2316 in FLNA, leading to von Hippel-Lindau (VHL)-mediated ubiquitination and proteasomal degradation. In hypoxia, PHD2 inactivation rapidly upregulates FLNA protein levels because of blockage of its proteasomal degradation. FLNA upregulation induces more immature spines, whereas Flna silencing rescues the immature spine phenotype induced by PHD2 inhibition.
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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.