title: A reduced number of metabotropic glutamate subtype 5 receptors are associated with constitutive homer proteins in a mouse model of fragile X syndrome.
abstract: Fragile X (FRAX) syndrome is a common inherited form of mental retardation resulting from the lack of fragile X mental retardation protein (FMRP) expression. The consequences of FMRP absence in the mechanism underlying mental retardation are unknown. Here, we tested the hypothesis that glutamate receptor (GluR) expression might be altered in FRAX syndrome. Initial in situ hybridization and Western blotting experiments did not reveal differences in mRNA levels and protein expression of AMPA and NMDA subunits and metabotropic glutamate subtype 5 (mGlu5) receptors between control and Fmr1 knock-out (KO) mice during postnatal development. However, a detergent treatment (1% Triton X-100) revealed a selective reduction of mGlu5 receptor expression in the detergent-insoluble fraction of synaptic plasma membranes (SPMs) from KO mice, with no difference in the expression of NR2A, GluR1, GluR2/3, GluR4, and Homer proteins. mGlu5 receptor expression was also lower in Homer immunoprecipitates from Fmr1 KO SPMs. Homer, but not NR2A, mGlu5, and GluR1, was found to be less tyrosine phosphorylated in Fmr1 KO than control mice. Our data indicate that, in FRAX syndrome, a reduced number of mGlu5 receptors are tightly linked to the constituents of postsynaptic density and, in particular, to the constitutive forms of Homer proteins, with possible consequent alterations in synaptic plasticity.
authors.affiliation: Department of Chemical Sciences, University of Catania, 95125 Catania, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Giuffrida
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Musumeci
authors.forename: Simona
authors.initials: S
authors.lastname: D'Antoni
authors.forename: Carmela Maria
authors.initials: CM
authors.lastname: Bonaccorso
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Giuffrida-Stella
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Maria Vincenza
authors.initials: MV
authors.lastname: Catania
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000378:metabolism*; D000072233:Homer Scaffolding Proteins; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009473:Neuronal Plasticity; D017830:Octoxynol; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D012995:Solubility; D013569:Synapses; D013570:Synaptic Membranes / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D000072233:Homer Scaffolding Proteins; D017830:Octoxynol; D020033:Protein Isoforms; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D014443:Tyrosine; C497684:Fmr1 protein, mouse