Skip to main content
Top
Published in: Molecular Autism 1/2013

Open Access 01-12-2013 | Letter to the Editor

Phosphorylated fragile X mental retardation protein at serine 499, is reduced in cerebellar vermis and superior frontal cortex of subjects with autism: implications for fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling

Authors: Øyvind G Rustan, Timothy D Folsom, Mahtab K Yousefi, S Hossein Fatemi

Published in: Molecular Autism | Issue 1/2013

Login to get access

Abstract

Lohith et al. (Mol Autism 4:15, 2013) recently identified increased metabotropic glutamate receptor 5 (mGluR5) expression in the frontal cortex (FC) of subjects with fragile X syndrome. These results are consistent with postmortem findings in cerebellar vermis and FC of subjects with autism (Fatemi and Folsom, Mol Autism 2:6, 2011; Fatemi et al. Anat Rec 294:1635–1645, 2011), suggesting that increased mGluR5 signaling is common to multiple autism spectrum disorders. Increased mGluR5 signaling may be associated with reduced phosphorylation of fragile X mental retardation protein (FMRP), which could result in the inactivation of this protein. In the current study, we report on reduced expression of phosphorylated FMRP in cerebellar vermis of adults and children with autism and in FC of adults with autism.
Appendix
Available only for authorised users
Literature
1.
go back to reference Lohith TG, Osterweil EK, Fujita M, Jenko KJ, Bear MF, Innis RB: Is metabotropic glutamate receptor 5 upregulated in prefrontal cortex in fragile X syndrome. Mol Autism. 2013, 4: 15-10.1186/2040-2392-4-15.PubMedCentralCrossRefPubMed Lohith TG, Osterweil EK, Fujita M, Jenko KJ, Bear MF, Innis RB: Is metabotropic glutamate receptor 5 upregulated in prefrontal cortex in fragile X syndrome. Mol Autism. 2013, 4: 15-10.1186/2040-2392-4-15.PubMedCentralCrossRefPubMed
2.
go back to reference Fatemi SH, Folsom TD: Dysregulation of fragile X mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of subjects with autism: a postmortem brain study. Mol Autism. 2011, 2: 6-10.1186/2040-2392-2-6.PubMedCentralCrossRefPubMed Fatemi SH, Folsom TD: Dysregulation of fragile X mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of subjects with autism: a postmortem brain study. Mol Autism. 2011, 2: 6-10.1186/2040-2392-2-6.PubMedCentralCrossRefPubMed
3.
go back to reference Fatemi SH, Folsom TD, Kneeland RE, Liesch SB: Metabotropic glutamate receptor 5 upregulation in children with autism is associated with underexpression of both fragile X mental retardation protein and GABAA receptor beta 3 in adults with autism. Anat Rec. 2011, 294: 1635-1645. 10.1002/ar.21299.CrossRef Fatemi SH, Folsom TD, Kneeland RE, Liesch SB: Metabotropic glutamate receptor 5 upregulation in children with autism is associated with underexpression of both fragile X mental retardation protein and GABAA receptor beta 3 in adults with autism. Anat Rec. 2011, 294: 1635-1645. 10.1002/ar.21299.CrossRef
4.
go back to reference Fatemi SH, Folsom TD, Rooney RJ, Thuras PD: mRNA and protein expression for novel GABAA receptors θ and ρ2 are altered in schizophrenia and mood disorders; relevance to FMRP-mGluR5 signaling pathway. Transl Psychiatry. 2013, 3: e271-10.1038/tp.2013.46. doi: 10.1038/tp.2013.46PubMedCentralCrossRefPubMed Fatemi SH, Folsom TD, Rooney RJ, Thuras PD: mRNA and protein expression for novel GABAA receptors θ and ρ2 are altered in schizophrenia and mood disorders; relevance to FMRP-mGluR5 signaling pathway. Transl Psychiatry. 2013, 3: e271-10.1038/tp.2013.46. doi: 10.1038/tp.2013.46PubMedCentralCrossRefPubMed
5.
go back to reference Krueger DD, Bear MF: The mGluR theory of fragile X syndrome. Autism spectrum disorders. Edited by: Amaral DG, Dawson G, Geschwind DH. 2011, New York: Oxford University Press, USA, 1239-1258.CrossRef Krueger DD, Bear MF: The mGluR theory of fragile X syndrome. Autism spectrum disorders. Edited by: Amaral DG, Dawson G, Geschwind DH. 2011, New York: Oxford University Press, USA, 1239-1258.CrossRef
6.
go back to reference Fatemi SH, Kneeland RE, Liesch SB, Folsom TD: Fragile X mental retardation protein levels are decreased in major psychiatric disorders. Schizophr Res. 2010, 124: 246-247. 10.1016/j.schres.2010.07.017.PubMedCentralCrossRefPubMed Fatemi SH, Kneeland RE, Liesch SB, Folsom TD: Fragile X mental retardation protein levels are decreased in major psychiatric disorders. Schizophr Res. 2010, 124: 246-247. 10.1016/j.schres.2010.07.017.PubMedCentralCrossRefPubMed
7.
go back to reference Fatemi SH, Folsom TD, Kneeland RE, Yousefi M, Liesch S, Thuras PD: Impairment of fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling and its downstream cognates ras-related C3 botulinum toxin substrate 1, amyloid beta A4 precursor protein, striatal-enriched protein tyrosine phosphatase, and homer 1, in autism: a postmortem study in cerebellar vermis and superior frontal cortex. Mol Autism. 2013, 4: 21-10.1186/2040-2392-4-21. doi: 10.1186/2040-2392-4-21PubMedCentralCrossRefPubMed Fatemi SH, Folsom TD, Kneeland RE, Yousefi M, Liesch S, Thuras PD: Impairment of fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling and its downstream cognates ras-related C3 botulinum toxin substrate 1, amyloid beta A4 precursor protein, striatal-enriched protein tyrosine phosphatase, and homer 1, in autism: a postmortem study in cerebellar vermis and superior frontal cortex. Mol Autism. 2013, 4: 21-10.1186/2040-2392-4-21. doi: 10.1186/2040-2392-4-21PubMedCentralCrossRefPubMed
8.
go back to reference Ceman S, O’Donnell WT, Reed M, Patton S, Pohl J, Warren ST: Phosphorylation influences the translation state of FMRP-associated polyribosomes. Hum Mol Genet. 2003, 12: 3295-3305. 10.1093/hmg/ddg350.CrossRefPubMed Ceman S, O’Donnell WT, Reed M, Patton S, Pohl J, Warren ST: Phosphorylation influences the translation state of FMRP-associated polyribosomes. Hum Mol Genet. 2003, 12: 3295-3305. 10.1093/hmg/ddg350.CrossRefPubMed
9.
go back to reference Nalavadi VC, Muddashetty RS, Gross C, Bassell GJ: Dephosphorylation-induced ubiquitination and degradation of FMRP in dendrites: a role in immediate early mGluR-stimulated translation. J Neurosci. 2012, 32: 2582-2587. 10.1523/JNEUROSCI.5057-11.2012.PubMedCentralCrossRefPubMed Nalavadi VC, Muddashetty RS, Gross C, Bassell GJ: Dephosphorylation-induced ubiquitination and degradation of FMRP in dendrites: a role in immediate early mGluR-stimulated translation. J Neurosci. 2012, 32: 2582-2587. 10.1523/JNEUROSCI.5057-11.2012.PubMedCentralCrossRefPubMed
Metadata
Title
Phosphorylated fragile X mental retardation protein at serine 499, is reduced in cerebellar vermis and superior frontal cortex of subjects with autism: implications for fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling
Authors
Øyvind G Rustan
Timothy D Folsom
Mahtab K Yousefi
S Hossein Fatemi
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2013
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/2040-2392-4-41

Other articles of this Issue 1/2013

Molecular Autism 1/2013 Go to the issue