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.
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There was no significant difference in NR2A, NR2B or p250GAP total protein levels between wild-type and FMR1 KO hippocampus at 7 and 14 days after birth.
“Consistent with previous reports (Giuffrida et al., 2005), we found no significant difference in NR2A, NR2B or p250GAP total protein levels between wild-type and KO (Supplemental Figure S8).”
From Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 (2010) · cites this paper as Giuffrida et al., 2005
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- Authors
- Giuffrida, R., Musumeci, S., D'Antoni, S., Bonaccorso, C. M., Giuffrida-Stella, A. M., Oostra, B. A., & Catania, M. V.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-09-28
- Volume
- 25
- Issue
- 39
- Pages
- 8908-8916
- ISSN
- 0270-6474
- 1529-2401
- Cited by
- 119
- References
- 9
- Language
- en
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