R. Araya, J. Jiang, K. B. Eisenthal, and R. Yuste, The spine neck filters membrane potentials, Proc. Natl. Acad. Sci. USA, vol.103, pp.17961-17966, 2006.

, Figure 7. The Effect of Filamin A Upregulation on Spine Maturation

, Representative IB for FLNA, myc, and actin in HEK293T cells under control or hypoxia (0.2% O 2 ) conditions or after transfection with mycFLNA D21-D23-WT (left). Also shown is densitometric quantification of FLNA

, Representative IB for myc and YFP after IP of myc in the presence of recombinant GST or GST-FLNA D21-D23 proteins from homogenates of HEK293T cells cotransfected with mycFLNA FL and PHD2 WT YFP. Left (input): total lysate control in co-transfected HEK293T cells. Densitometric quantification of the PHD2 WT YFP/ mycFLNA FL ratio is shown

. -h), Representative images of tdT + 14-DIV ctrl (C), mycFLNA D21-D23-WT (D), or mycFLNA D21-D23-3P/A (E) transfected MHNs. Also shown is quantification of protrusion density (F), protrusion length (G), and percentage of spines with a head (H) (n = 10 neurons, pp.324-731

, PSD-95 (red) (I 0 , J 0 , and K 0 ) in 21-DIV tdT-transfected MHN (I-K) alone (I and I 0 ) or together with mycFLNA D21-D23-WT (J and J 0 ) or mycFLNA D21-D23-3P/A (K and K 0 ). The contours of the dendrites in (I), (J), and (K) are indicated in (I 0 ), -K 0 ) Immunostaining of vGlut (green)

, Quantification of the dendritic density of vGlut + /PSD-95 + co-clusters

, Representative images of 14-DIV MHNs co-transfected with tdT together with scrambled control shRNA (M), shPhd2 (N), shFlna (O), or both shPhd2 and shFlna (P)

, Quantification of protrusion density (Q), protrusion length (R), and percentage of spines with a head

, Data are mean ± SEM. *p < 0.05, ***p < 0.001 versus ctrl or scr

F. V. Bolduc, K. Bell, C. Rosenfelt, H. Cox, and T. Tully, , 2010.

C. E. Brown, J. D. Boyd, and T. H. Murphy, , 2010.

K. O. Cho, C. A. Hunt, and M. B. Kennedy, , 1992.

A. Corcoran, R. Kunze, S. C. Harney, G. Breier, H. H. Marti et al., A role for prolyl hydroxylase domain proteins in hippocampal synaptic plasticity, Hippocampus, vol.23, pp.861-872, 2013.

A. C. Epstein, J. M. Gleadle, L. A. Mcneill, K. S. Hewitson, J. O&apos;rourke et al., , 2001.

M. Ereci-nska and I. A. Silver, Tissue oxygen tension and brain sensitivity to hypoxia, Respir. Physiol, vol.128, pp.263-276, 2001.

I. M. Ethell, P. , and E. B. , Molecular mechanisms of dendritic spine development and remodeling, Prog. Neurobiol, vol.75, pp.161-205, 2005.

S. Gaillard, Y. Bailly, M. Benoist, T. Rakitina, J. P. Kessler et al., Targeting of proteins of the striatin family to dendritic spines: role of the coiled-coil domain, Traffic, vol.7, pp.74-84, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00092658

L. Gambazzi, O. Gokce, T. Seredenina, E. Katsyuba, H. Runne et al., Diminished activity-dependent brain-derived neurotrophic factor expression underlies cortical neuron microcircuit hypoconnectivity resulting from exposure to mutant huntingtin fragments, J. Pharmacol. Exp. Ther, vol.335, pp.13-22, 2010.

P. Hotulainen and C. C. Hoogenraad, Actin in dendritic spines: connecting dynamics to function, J. Cell Biol, vol.189, pp.619-629, 2010.

M. Ivan, K. Kondo, H. Yang, W. Kim, J. Valiando et al., HIFalpha targeted for VHLmediated destruction by proline hydroxylation: implications for O2 sensing, Science, vol.292, pp.464-468, 2001.

P. Jaakkola, D. R. Mole, Y. M. Tian, M. I. Wilson, J. Gielbert et al.,

, Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation, Science, vol.292, pp.468-472

M. Mazzone, D. Dettori, R. Leite-de-oliveira, S. Loges, T. Schmidt et al., , 2009.

R. Meller, S. J. Thompson, T. A. Lusardi, A. N. Ordonez, M. D. Ashley et al., , 2008.

, Ubiquitin proteasome-mediated synaptic reorganization: a novel mechanism underlying rapid ischemic tolerance, J. Neurosci, vol.28, pp.50-59

F. Nakamura, T. P. Stossel, and J. H. Hartwig, The filamins: organizers of cell structure and function, Cell Adhes. Migr, vol.5, pp.160-169, 2011.

M. W. Nestor, X. Cai, M. R. Stone, R. J. Bloch, and S. M. Thompson, , 2011.

, The actin binding domain of bI-spectrin regulates the morphological and functional dynamics of dendritic spines, PLoS ONE, vol.6, 16197.

Y. Noam, L. Phan, S. Mcclelland, E. M. Manders, M. U. Ehrengruber et al., Distinct regional and subcellular localization of the actin-binding, 2012.

, J. Comp. Neurol, vol.520, pp.3013-3034

E. Nwabuisi-heath, M. J. Ladu, Y. , and C. , , 2012.

A. Oruganty-das, T. Ng, T. Udagawa, E. L. Goh, and J. D. Richter, Translational control of mitochondrial energy production mediates neuron morphogenesis, Cell Metab, vol.16, pp.789-800, 2012.

E. Pacary, M. A. Haas, H. Wildner, R. Azzarelli, D. M. Bell et al., Visualization and genetic manipulation of dendrites and spines in the mouse cerebral cortex and hippocampus using in utero electroporation, J. Vis. Exp, vol.26, p.4163, 2012.

S. Reinartz, I. Biro, A. Gal, M. Giugliano, and S. Marom, Synaptic dynamics contribute to long-term single neuron response fluctuations, Front. Neural Circuits, vol.8, p.71, 2014.

M. R. Sarkisian, C. M. Bartley, H. Chi, F. Nakamura, K. Hashimoto-torii et al., MEKK4 signaling regulates filamin expression and neuronal migration, Neuron, vol.52, pp.789-801, 2006.

I. Segura, C. L. Essmann, S. Weinges, and A. Acker-palmer, Grb4 and GIT1 transduce ephrinB reverse signals modulating spine morphogenesis and synapse formation, Nat. Neurosci, vol.10, pp.301-310, 2007.

D. Song, L. S. Li, K. J. Heaton-johnson, P. R. Arsenault, S. R. Master et al., Prolyl hydroxylase domain protein 2 (PHD2) binds a Pro-Xaa-Leu-Glu motif, linking it to the heat shock protein 90 pathway, J. Biol. Chem, vol.288, pp.9662-9674, 2013.

T. P. Stossel, J. Condeelis, L. Cooley, J. H. Hartwig, A. Noegel et al., Filamins as integrators of cell mechanics and signalling, Nat. Rev. Mol. Cell Biol, vol.2, pp.138-145, 2001.

A. Tashiro and R. Yuste, Regulation of dendritic spine motility and stability by Rac1 and Rho kinase: evidence for two forms of spine motility, Mol. Cell. Neurosci, vol.26, pp.429-440, 2004.

H. Tsuchiya, T. Iseda, and O. Hino, Identification of a novel protein (VBP-1) binding to the von Hippel-Lindau (VHL) tumor suppressor gene product, Biochim. Biophys. Acta, vol.56, pp.99-117, 1996.

S. Vogel, M. Wottawa, K. Farhat, A. Zieseniss, M. Schnelle et al., Prolyl hydroxylase domain (PHD) 2 affects cell migration and F-actin formation via RhoA/rho-associated kinase-dependent cofilin phosphorylation, J. Biol. Chem, vol.285, pp.33756-33763, 2010.

B. W. Wong, A. Kuchnio, U. Bruning, and P. Carmeliet, Emerging novel functions of the oxygen-sensing prolyl hydroxylase domain enzymes, Trends Biochem. Sci, vol.38, pp.3-11, 2013.

J. Zhang, J. Neal, G. Lian, B. Shi, R. J. Ferland et al., Brefeldin A-inhibited guanine exchange factor 2 regulates filamin A phosphorylation and neuronal migration, J. Neurosci, vol.32, pp.12619-12629, 2012.

J. Zhang, J. Neal, G. Lian, J. Hu, J. Lu et al., Filamin A regulates neuronal migration through brefeldin A-inhibited guanine exchange factor 2-dependent Arf1 activation, J. Neurosci, vol.33, pp.15735-15746, 2013.

L. Zhang, C. M. Bartley, X. Gong, L. S. Hsieh, T. V. Lin et al., MEK-ERK1/2-dependent FLNA overexpression promotes abnormal dendritic patterning in tuberous sclerosis independent of mTOR, Neuron, vol.84, pp.78-91, 2014.

L. Zheng, Y. Michelson, V. Freger, Z. Avraham, K. J. Venken et al., Drosophila Ten-m and filamin affect motor neuron growth cone guidance, PLoS ONE, vol.6, 2011.

X. Zheng, A. X. Zhou, P. Rouhi, H. Uramoto, J. Boré-n et al., Hypoxia-induced and calpain-dependent cleavage of filamin A regulates the hypoxic response, Proc. Natl. Acad. Sci. USA, vol.111, pp.2560-2565, 2014.

A. X. Zhou, J. H. Hartwig, and L. M. Aky?-urek, Filamins in cell signaling, transcription and organ development, Trends Cell Biol, vol.20, pp.113-123, 2010.