A reduced number of metabotropic glutamate subtype 5 receptors are associated with constitutive Homer proteins in a mouse model of fragile X syndrome

Raffaella Giuffrida, Sebastiano Musumeci, Simona D'Antoni, Carmela Maria Bonaccorso, Anna Maria Giuffrida-Stella, Ben A. Oostra, Maria Vincenza Catania

Research output: Contribution to journalArticle

99 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8908-8916
Number of pages9
JournalJournal of Neuroscience
Volume25
Issue number39
DOIs
Publication statusPublished - Sep 28 2005

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Metabotropic Glutamate 5 Receptor
Fragile X Syndrome
Fragile X Mental Retardation Protein
Knockout Mice
Synaptic Membranes
Intellectual Disability
Detergents
Cell Membrane
Post-Synaptic Density
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Neuronal Plasticity
Octoxynol
Glutamate Receptors
N-Methylaspartate
In Situ Hybridization
Tyrosine
Glutamic Acid
Western Blotting
Messenger RNA
Homer Scaffolding Proteins

Keywords

  • Glutamate receptors
  • Homer
  • Mental retardation
  • Synaptic plasticity
  • Synaptosomes
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A reduced number of metabotropic glutamate subtype 5 receptors are associated with constitutive Homer proteins in a mouse model of fragile X syndrome. / Giuffrida, Raffaella; Musumeci, Sebastiano; D'Antoni, Simona; Bonaccorso, Carmela Maria; Giuffrida-Stella, Anna Maria; Oostra, Ben A.; Catania, Maria Vincenza.

In: Journal of Neuroscience, Vol. 25, No. 39, 28.09.2005, p. 8908-8916.

Research output: Contribution to journalArticle

Giuffrida, Raffaella ; Musumeci, Sebastiano ; D'Antoni, Simona ; Bonaccorso, Carmela Maria ; Giuffrida-Stella, Anna Maria ; Oostra, Ben A. ; Catania, Maria Vincenza. / A reduced number of metabotropic glutamate subtype 5 receptors are associated with constitutive Homer proteins in a mouse model of fragile X syndrome. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 39. pp. 8908-8916.
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