Agonistindependent activation of metabotropic glutamate receptors by the intracellular protein Homer, Nature, vol.411, pp.962-965, 2001. ,
URL : https://hal.archives-ouvertes.fr/inserm-00318959
Excitatory/inhibitory synaptic imbalance leads to hippocampal hyperexcitability in mouse models of tuberous sclerosis, Neuron, vol.78, pp.510-522, 2013. ,
Characterization of the proteome, diseases and evolution of the human postsynaptic density, Nat Neurosci, vol.14, pp.19-21, 2011. ,
Dysregulation of group-I metabotropic glutamate (mGlu) receptor mediated signalling in disorders associated with Intellectual Disability and Autism, Neuroscience and biobehavioral reviews, 2014. ,
The translation of translational control by FMRP: therapeutic targets for FXS, Nat Neurosci, vol.16, pp.1530-1536, 2013. ,
FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism, Cell, vol.146, pp.247-261, 2011. ,
Synaptic, transcriptional and chromatin genes disrupted in autism, Nature, vol.515, pp.209-215, 2014. ,
Progress toward treatments for synaptic defects in autism, Nature medicine, vol.19, pp.685-694, 2013. ,
URL : https://hal.archives-ouvertes.fr/pasteur-01470299
Correction of fragile X syndrome in mice, Neuron, vol.56, pp.955-962, 2007. ,
A reduced number of metabotropic glutamate subtype 5 receptors are associated with constitutive homer proteins in a mouse model of fragile X syndrome, J Neurosci, vol.25, pp.8908-8916, 2005. ,
Excess phosphoinositide 3-kinase subunit synthesis and activity as a novel therapeutic target in fragile X syndrome, J Neurosci, vol.30, pp.10624-10638, 2010. ,
Tetrameric hub structure of postsynaptic scaffolding protein homer, J Neurosci, vol.26, pp.8492-8501, 2006. ,
The postsynaptic density proteins Homer and Shank form a polymeric network structure, Cell, vol.137, pp.159-171, 2009. ,
Altered Neocortical Rhythmic Activity States in Fmr1 KO Mice Are Due to Enhanced mGluR5 Signaling and Involve Changes in Excitatory Circuitry, J Neurosci, vol.31, pp.14223-14234, 2011. ,
CaMKII: claiming center stage in postsynaptic function and organization, Neuron, vol.81, pp.249-265, 2014. ,
Homeostatic Scaling Requires Group I mGluR Activation Mediated by Homer1a, Neuron, vol.68, pp.1128-1142, 2010. ,
NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins, Science, vol.319, pp.476-481, 2008. ,
The contribution of de novo coding mutations to autism spectrum disorder, Nature, vol.515, pp.216-221, 2014. ,
Crystal structure of the Homer 1 family conserved region reveals the interaction between the EVH1 domain and own proline-rich motif, J Mol Biol, vol.318, pp.1117-1126, 2002. ,
Differential regulation of CaMKII?lpha interactions with mGluR5 and NMDA receptors by Ca(2+) in neurons, J Neurochem, vol.127, pp.620-631, 2013. ,
Uncoupling of the endocannabinoid signalling complex in a mouse model of fragile X syndrome, Nature communications, vol.3, p.1080, 2012. ,
URL : https://hal.archives-ouvertes.fr/hal-01826158
High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism, PloS one, vol.7, p.35003, 2012. ,
Fragile X syndrome: a review of associated medical problems, Pediatrics, vol.134, pp.995-1005, 2014. ,
Phosphate-binding tag, a new tool to visualize phosphorylated proteins, Molecular & cellular proteomics : MCP, vol.5, pp.749-757, 2006. ,
Phosphorylation of group I metabotropic glutamate receptors (mGluR1/5) in vitro and in vivo, Neuropharmacology, vol.55, pp.403-408, 2008. ,
Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice, Neuron, vol.74, pp.49-56, 2012. ,
Phosphorylation of Homer3 by calcium/calmodulin-dependent kinase II regulates a coupling state of its target molecules in Purkinje cells, J Neurosci, vol.28, pp.5369-5382, 2008. ,
Dynamic remodeling of scaffold interactions in dendritic spines controls synaptic excitability, The Journal of cell biology, vol.198, pp.251-263, 2012. ,
Rapid redistribution of the postsynaptic density protein PSD-Zip45 (Homer 1c) and its differential regulation by NMDA receptors and calcium channels, J Neurosci, vol.21, pp.9561-9571, 2001. ,
Lovastatin corrects excess protein synthesis and prevents epileptogenesis in a mouse model of fragile X syndrome, Neuron, vol.77, pp.243-250, 2013. ,
Hypersensitivity to mGluR5 and ERK1/2 Leads to Excessive Protein Synthesis in the Hippocampus of a Mouse Model of Fragile X Syndrome, J Neurosci, vol.30, pp.15616-15627, 2010. ,
Changes in mGlu5 receptor-dependent synaptic plasticity and coupling to homer proteins in the hippocampus of Ube3A hemizygous mice modeling angelman syndrome, J Neurosci, vol.34, pp.4558-4566, 2014. ,
Altered cerebral protein synthesis in fragile X syndrome: studies in human subjects and knockout mice, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, vol.33, pp.499-507, 2013. ,
Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome, Nat Neurosci, vol.15, 2012. ,
Homer interactions are necessary for metabotropic glutamate receptor-induced long-term depression and translational activation, J Neurosci, vol.28, pp.543-547, 2008. ,
Auditory processing in fragile x syndrome, Frontiers in cellular neuroscience, vol.8, p.19, 2014. ,
The Homer family proteins, Genome Biol, vol.8, p.206, 2007. ,
Interaction of Cupidin/Homer2 with two actin cytoskeletal regulators, Cdc42 small GTPase and Drebrin, in dendritic spines, BMC neuroscience, vol.10, p.25, 2009. ,
CaMKII: a molecular substrate for synaptic plasticity and memory, Prog Mol Biol Transl Sci, vol.122, pp.61-87, 2014. ,
Deficient hippocampal long-term potentiation in alphacalcium-calmodulin kinase II mutant mice, Science, vol.257, pp.201-206, 1992. ,
No evidence for disruption of normal patterns of mRNA localization in dendrites or dendritic transport of recently synthesized mRNA in FMR1 knockout mice, a model for human fragile-X mental retardation syndrome, Neuroreport, vol.9, pp.477-481, 1998. ,
Homer protein-metabotropic glutamate receptor binding regulates endocannabinoid signaling and affects hyperexcitability in a mouse model of fragile x syndrome, J Neurosci, vol.35, pp.3938-3945, 2015. ,
Functional consequences of mutations in postsynaptic scaffolding proteins and relevance to psychiatric disorders. Annual review of neuroscience, vol.35, pp.49-71, 2012. ,
Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of alphaCaMKII inhibitory phosphorylation, Nat Neurosci, vol.10, pp.280-282, 2007. ,
Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins, Neuron, vol.21, pp.707-716, 1998. ,
The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses, Cell, vol.112, pp.317-327, 2003. ,
Enhanced endocannabinoid signaling elevates neuronal excitability in fragile X syndrome, J Neurosci, vol.30, pp.5724-5729, 2010. ,
Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1(?/y) mice, Nat Neurosci, vol.17, pp.1701-1709, 2014. ,
URL : https://hal.archives-ouvertes.fr/hal-02064702
, C) Pharmacological blockade of NMDA receptors and L-VGCCs inhibits brief PTXinduced dissociation of mGluR5-Homer in WT cultures, as assessed by co-IP. The specific inhibitors: NMDA receptor, p.5
Voltage gated Calcium channel: nimodipine; mGluR5: MPEP; mGluR1: LY367385. n=4 ,
, D) Pharmacological blockade of CaMKII inhibits brief PTX-induced dissociation of mGluR5-Homer in WT cultures, as assessed by co-IP. The specific inhibitors tested are: CaMKII: KN-93 and CaMKIINtide
, Co-expression of a shRNA-resistant CaMKII? (CaMKII?res) rescues PTX-induced decreases in mGluR5-Homer. n=5. All experiments are repeated in at least 3 independent cultures. In all figures, error bars represent SEM
, C) Knockdown of endogenous H1 and H2 and replacement of H2 with a myc-tagged dephosphomimetic (S117/S216AA) prevents activity-induced dissociation of mGluR5-Homer cortical neurons
, Representative dendritic spine images (left to right) of Homer3-Venus fluorescence, mGlu5-luc emission (Em) at 480, Em535 from Homer-Venus as a result of BRET from mGluR5luc, and Em535/480 ratio. Scale bar= 1 µM. Red line indicates region of quantification of BRET of spine and dendritic shaft
Brief depolarization (5 min; 55mM KCl) of WT neurons transfected with wildtype Homer3-Venus reduces the mGluR5-Homer BRET in spines ,
, , p.23
, Author manuscript; available in PMC, Cell Rep, 2015.
WT neurons expressing a dephosphomimetic Homer3(AAA)-Venus display normal spine BRET under basal (3mM KCl) conditions, but no change in BRET in response to 55mM KCl ,
neurons expressing a phosphomimetic Homer3(DDD)-Venus display reduced spine BRET under basal (3mM KCl) conditions, and no change in BRET in response to 55mM KCl ,
KO neurons expressing Homer3-Venus show reduced BRET in spines under basal conditions ,
Group spine BRET values from each condition. n = 3 cultures and 8-16 spines/condition ,
, C) Total and phosphorylated (T286) CaMKII? levels are elevated in total lysates and PSD fractions from Fmr1 KO cortex
, Knockdown of CaMKII? (shCaMKII?) restores mGluR5-Homer interactions in cultured Fmr1 KO cortical neurons in comparison to control shRNA (shCtrl) transfected cultures. Blots of mGluR5 after co-IP with Homer, p.4
Inhibition of CaMKII activity by KN93 rescues prolonged neocortical UP states in Fmr1 KO neocortical slices. Left: Representative traces of UP states from each condition ,
, D) Genetic reduction of CaMKII? in Fmr1 KO/CaMKII? +/? mice rescues mGluR5-Homer interaction in Fmr1 KO mice. The front cortex tissue lysates were from WT/WT, p.1
Western blots of mGluR5 after coimmunoprecipitation (IP) with Homer antibody (top) ,
? mice rescues audiogenic seizures. Fmr1 KO mice had an increased seizure score, the audiogenic seizure score was reduced in Fmr1 KO/ CaMKII? +/? mice (n = 35, 37, 28 and 21 mice for ,