Skip to Main content Skip to Navigation
Journal articles

The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A

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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [49 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-02573601
Contributor : Virginie Portelette <>
Submitted on : Thursday, May 14, 2020 - 2:06:58 PM
Last modification on : Tuesday, June 16, 2020 - 4:12:03 PM

File

Oxygen Sensor PHD2 Controls De...
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License

Identifiers

Collections

Citation

Inmaculada Segura, Christian Lange, Ellen Knevels, Anastasiya Moskalyuk, Rocco Pulizzi, et al.. The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A. Cell Reports, Elsevier Inc, 2016, 14 (11), pp.2653-2667. ⟨10.1016/j.celrep.2016.02.047⟩. ⟨pasteur-02573601⟩

Share

Metrics

Record views

43

Files downloads

91