The fragile X mental retardation protein is associated with poly(A)+ mRNA in actively translating polyribosomes

Corbin, François; Bouillon, Marlène; Fortin, Anny; Morin, S.H.X.; Rousseau, François; Khandjian, Édouard W.

doi:10.1093/hmg/6.9.1465

Cited by 220 publications

(164 citation statements)

References 35 publications

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“…In brain, FMRP is seen in cytoplasm both in neuronal somata and dendrites (Devys et al, 1993;Feng et al, 1997). FMRP forms complexes with other proteins, including two FMRP homologs, the fragile X-related proteins 1 and 2 (FXR1P and FXR2P), along with mRNA in association with ribosomes (Eberhart et al, 1996;Khandjian et al, 1996;Corbin et al, 1997;Feng et al, 1997;Ceman et al, 1999). In in vitro experiments, binding of FMRP to RNA appears to inhibit translation (Laggerbauer et al, 2001;Li et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Age-Dependent and Selective Impairment of Long-Term Potentiation in the Anterior Piriform Cortex of Mice Lacking the Fragile X Mental Retardation Protein

Larson¹,

Jessen²,

Kim³

et al. 2005

J. Neurosci.

121

112

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Synaptic function and plasticity were studied in mice lacking the fragile X mental retardation protein (FMRP), a model for the fragile X mental retardation syndrome. Associational connections were studied in slices of anterior piriform (olfactory) cortex, and Schaffercommissural synapses were studied in slices of hippocampus. Knock-out (KO) mice lacking FMRP were compared with congenic C57BL/6J wild-type (WT) controls. Input-output curves and paired-pulse plasticity were not significantly altered in KO compared with WT mice in either the olfactory cortex or hippocampus. Long-term potentiation (LTP) induced by theta burst stimulation in the anterior piriform cortex was normal in KO mice aged Ͻ6 months but was impaired in KO mice aged Ͼ6 months. The deficit in LTP was significant in mice aged 6 -12 months and more pronounced in mice aged 12-18 months. Similar differences between WT and KO mice were seen whether LTP was induced in the presence or absence of a GABA A receptor blocker. Postsynaptic responses to patterned burst stimulation in KO mice showing impaired LTP were not significantly different from those in WT mice, suggesting that the LTP deficit was not caused by alterations in circuit properties. No differences in hippocampal LTP were observed in WT and KO mice at any ages. The results indicate that FMRP deficiency is associated with an age-dependent and region-selective impairment in long-term synaptic plasticity.

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Section: Discussionmentioning

confidence: 99%

Age-Dependent and Selective Impairment of Long-Term Potentiation in the Anterior Piriform Cortex of Mice Lacking the Fragile X Mental Retardation Protein

Larson¹,

Jessen²,

Kim³

et al. 2005

J. Neurosci.

121

112

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“…For these, FMRP can suppress translation [e.g., FMRP interacts with the murine MAP1B or its Drosophila homolog Futsch, and both exhibit enhanced expression in mouse and fly Fmr1 knock-outs (KOs)] as expected in the absence of FMRP translational suppression (Zhang et al, 2001;Lu et al, 2004). Consistent with its influence over translation, FMRP associates with polysomes, especially intriguing in dendritic spines, because abnormal spine structure is one morphological feature seen consistently in both fragile X patients and the mouse model (Corbin et al, 1997;Feng et al, 1997a,b;Stefani et al, 2004). This indicates a role for FMRP in synaptic protein synthesis supported by the effect of group I metabotropic glutamate receptor (mGluR1/5) signaling on FMRP synthesis and transport (Antar et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

FMRP Phosphorylation Reveals an Immediate-Early Signaling Pathway Triggered by Group I mGluR and Mediated by PP2A

Narayanan¹,

Nalavadi²,

Nakamoto³

et al. 2007

J. Neurosci.

205

248

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Fragile X syndrome is a common form of inherited mental retardation and is caused by loss of fragile X mental retardation protein (FMRP), a selective RNA-binding protein that influences the translation of target messages. Here, we identify protein phosphatase 2A (PP2A) as an FMRP phosphatase and report rapid FMRP dephosphorylation after immediate group I metabotropic glutamate receptor (mGluR) stimulation (Ͻ1 min) in neurons caused by enhanced PP2A enzymatic activity. In contrast, extended mGluR activation (1-5 min) resulted in mammalian target of rapamycin (mTOR)-mediated PP2A suppression and FMRP rephosphorylation. These activitydependent changes in FMRP phosphorylation were also observed in dendrites and showed a temporal correlation with the translational profile of select FMRP target transcripts. Collectively, these data reveal an immediate-early signaling pathway linking group I mGluR activity to rapid FMRP phosphorylation dynamics mediated by mTOR and PP2A.

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“…The FMR1 protein preferentially binds to poly(G), poly(U) and a subset of brain mRNAs in vitro (Ashley et al, 1993;Siomi et al, 1993;Brown et al, 1998). In addition, FMR1 is associated with polyribosomes and a large number of mRNAs in vivo, some of which contain G quartet structures as FMR1-binding motifs (Feng et al, 1997a;Corbin et al, 1997;Sung et al, 2000;Darnell et al, 2001;Brown et al, 2001;Zalfa et al, 2003;Miyashiro et al, 2003). It remains to be determined which proteins encoded by mRNAs in FMR1-mRNP complexes are primarily responsible for the morphological and functional deficits caused by the absence of FMR1.…”

Section: Introductionmentioning

confidence: 99%

Control of dendritic development by theDrosophila fragile X-relatedgene involves the small GTPase Rac1

et al. 2003

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Fragile X syndrome is caused by loss-of-function mutations in the fragile X mental retardation 1 gene. How these mutations affect neuronal development and function remains largely elusive. We generated specific point mutations or small deletions in the Drosophila fragile X-related (Fmr1) gene and examined the roles of Fmr1 in dendritic development of dendritic arborization (DA) neurons in Drosophila larvae. We found that Fmr1 could be detected in the cell bodies and proximal dendrites of DA neurons and that Fmr1loss-of-function mutations increased the number of higher-order dendritic branches. Conversely, overexpression of Fmr1 in DA neurons dramatically decreased dendritic branching. In dissecting the mechanisms underlying Fmr1 function in dendrite development, we found that the mRNA encoding small GTPase Rac1 was present in the Fmr1-messenger ribonucleoprotein complexes in vivo. Mosaic analysis with a repressor cell marker (MARCM) and overexpression studies revealed that Rac1 has a cell-autonomous function in promoting dendritic branching of DA neurons. Furthermore, Fmr1 and Rac1 genetically interact with each other in controlling the formation of fine dendritic branches. These findings demonstrate that Fmr1 affects dendritic development and that Rac1 is partially responsible for mediating this effect.

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The fragile X mental retardation protein is associated with poly(A)+ mRNA in actively translating polyribosomes

Cited by 220 publications

References 35 publications

Age-Dependent and Selective Impairment of Long-Term Potentiation in the Anterior Piriform Cortex of Mice Lacking the Fragile X Mental Retardation Protein

Age-Dependent and Selective Impairment of Long-Term Potentiation in the Anterior Piriform Cortex of Mice Lacking the Fragile X Mental Retardation Protein

FMRP Phosphorylation Reveals an Immediate-Early Signaling Pathway Triggered by Group I mGluR and Mediated by PP2A

Control of dendritic development by theDrosophila fragile X-relatedgene involves the small GTPase Rac1

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