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Journal articles
The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A
Inmaculada Segura
1, 2
Christian Lange
1, 2
Ellen Knevels
1, 2
Anastasiya Moskalyuk
3
Rocco Pulizzi
3
Guy Eelen
1, 2
Thibault Chaze
4
Cicerone Tudor
5
Cyril Boulègue
4
Matthew Holt
5
Dirk Daelemans
6
Mariette Matondo
4
Bart Ghesquière
2
Michele Giugliano
3, 7, 8
Carmen Ruiz de almodovar
1, 2
Mieke Dewerchin
1, 2
Peter Carmeliet
1, 2, *
*
Corresponding author
1
VIB-CCB - Laboratory of Angiogenesis and Vascular Metabolism [Leuven, Belgium]
Department of Oncology [Leuven, Belgium]
4
Plateforme de Protéomique / Proteomics platform
UTechS MSBio - Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology
Inmaculada Segura 1, 2
Author
Christian Lange 1, 2
Author
Ellen Knevels 1, 2
Author
Anastasiya Moskalyuk 3
Author
Cyril Boulègue 4
Author
Matthew Holt 5
Author
Dirk Daelemans 6
Author
Mariette Matondo 4
Author IdHAL : mariette-matondo ORCID : https://orcid.org/0000-0003-3958-7710
Bart Ghesquière 2
Author
Michele Giugliano 3, 7, 8
Author
Carmen Ruiz de almodovar 1, 2
Author
Mieke Dewerchin 1, 2
Author
Peter Carmeliet 1, 2
Correspondent author
1
VIB-CCB - Laboratory of Angiogenesis and Vascular Metabolism [Leuven, Belgium] (Department of Oncology - ON IV Herestraat 49 - box 912, 3000 Leuven - Belgium)
- Department of Oncology [Leuven, Belgium] (KU Leuven
Herestraat 49, O&N1 box 818
B-3000 Leuven, Belgium - Belgium)
- KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven (Oude Markt 13 - bus 5005, 3000 Leuven - Belgium)
2
VRC - VIB Vesalius Research Center (Herestraat 49, Gasthuisberg O&N1, B3000 Leuven, Belgium - Belgium)
- KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven (Oude Markt 13 - bus 5005, 3000 Leuven - Belgium)
3
Universiteit Antwerpen [Antwerpen] ( Prinsstraat 13, 2000 Antwerpen - Belgium)
4
Plateforme de Protéomique / Proteomics platform (Département Biologie structurale et Chimie
25-28, rue du Docteur Roux
75724 Paris cedex 15 - France)
- UTechS MSBio - Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (Département Biologie structurale et Chimie
25-28, rue du Docteur Roux
75724 Paris cedex 15 - France)
- C2RT - Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (28 rue du Docteur Roux 75724 Paris Cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- CNRS - Centre National de la Recherche Scientifique : USR2000 (France)
- C2RT - Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (28 rue du Docteur Roux 75724 Paris Cedex 15 - France)
5
Laboratory of Glia Biology [Leuven, Belgium] (VIB-KU Leuven - ON IV Herestraat 49 - box 602, 3000 Leuven - Belgium)
- VIB-KU-CCB - Leuven Center for Cancer Biology (Campus Gasthuisberg of the University of Leuven -
Onderwijs & Navorsing 4 - Building 404-24
Herestraat 49, box 912 - 3000 Leuven, Belgium - Belgium)
- KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven (Oude Markt 13 - bus 5005, 3000 Leuven - Belgium)
- VIB - Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (Falnders Institute for Biotechnology - Rijvisschestraat 120, 9052, Belgique - Belgium)
6
Rega Institute for Medical Research [Leuven, België] (Minderbroedersstraat 10, B 3000 Leuven - Belgium)
- KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven (Oude Markt 13 - bus 5005, 3000 Leuven - Belgium)
7
NERF - Neuroelectronics Research Flanders (Kapeldreef 75, 3001 Leuven - Belgium)
8
BMI - EPFL - Brain Mind Institute (Faculty of Life Science, Ecole Polytechnique Federale de Lausanne (EPFL), EPFL-SV-BMI-LSENS, Station 19, CH-1015 Lausanne, Switzerland. - Switzerland)
- EPFL - Ecole Polytechnique Fédérale de Lausanne (CH-1015 Lausanne, Switzerland - Switzerland)
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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Contributor : Virginie Portelette <>
Submitted on : Thursday, May 14, 2020 - 2:06:58 PM
Last modification on : Tuesday, June 16, 2020 - 4:12:03 PM
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Oxygen Sensor PHD2 Controls De...
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- HAL Id : pasteur-02573601, version 1
- DOI : 10.1016/j.celrep.2016.02.047
- PUBMED : 26972007
- PUBMEDCENTRAL : PMC4805856
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⟩
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