PMID- 22268788
OWN - NLM
STAT- MEDLINE
DCOM- 20120910
LR  - 20231120
IS  - 1601-183X (Electronic)
IS  - 1601-1848 (Print)
IS  - 1601-183X (Linking)
VI  - 11
IP  - 3
DP  - 2012 Apr
TI  - Altered mTOR signaling and enhanced CYFIP2 expression levels in subjects with 
      fragile X syndrome.
PG  - 332-41
LID - 10.1111/j.1601-183X.2012.00768.x [doi]
AB  - Fragile X syndrome (FXS) is the most common form of inherited intellectual 
      disability and autism. The protein (FMRP) encoded by the fragile X mental 
      retardation gene (FMR1), is an RNA-binding protein linked to translational 
      control. Recently, in the Fmr1 knockout mouse model of FXS, dysregulated 
      translation initiation signaling was observed. To investigate whether an altered 
      signaling was also a feature of subjects with FXS compared to typical developing 
      controls, we isolated total RNA and translational control proteins from 
      lymphocytes of subjects from both groups (38 FXS and 14 TD). Although we did not 
      observe any difference in the expression level of messenger RNAs (mRNAs) for 
      translational initiation control proteins isolated from participant with FXS, we 
      found increased phosphorylation of the mammalian target of rapamycin (mTOR) 
      substrate, p70 ribosomal subunit 6 kinase1 (S6K1) and of the mTOR regulator, the 
      serine/threonine protein kinase (Akt), in their protein lysates. In addition, we 
      observed increased phosphorylation of the cap binding protein eukaryotic 
      initiation factor 4E (eIF4E) suggesting that protein synthesis is upregulated in 
      FXS. Similar to the findings in lymphocytes, we observed increased 
      phosphorylation of S6K1 in brain tissue from patients with FXS (n = 4) compared 
      to normal age-matched controls (n = 4). Finally, we detected increased expression 
      of the cytoplasmic FMR1-interacting protein 2 (CYFIP2), a known FMRP interactor. 
      This data verify and extend previous findings using lymphocytes for studies of 
      neuropsychiatric disorders and provide evidence that misregulation of mTOR 
      signaling observed in the FXS mouse model also occurs in human FXS and may 
      provide useful biomarkers for designing targeted treatments in FXS.
CI  - (c) 2012 The Authors. Genes, Brain and Behavior (c) 2012 Blackwell Publishing Ltd and 
      International Behavioural and Neural Genetics Society.
FAU - Hoeffer, C A
AU  - Hoeffer CA
AD  - Center for Neural Science, New York University, New York, NY, USA.
FAU - Sanchez, E
AU  - Sanchez E
FAU - Hagerman, R J
AU  - Hagerman RJ
FAU - Mu, Y
AU  - Mu Y
FAU - Nguyen, D V
AU  - Nguyen DV
FAU - Wong, H
AU  - Wong H
FAU - Whelan, A M
AU  - Whelan AM
FAU - Zukin, R S
AU  - Zukin RS
FAU - Klann, E
AU  - Klann E
FAU - Tassone, F
AU  - Tassone F
LA  - eng
GR  - NS047834/NS/NINDS NIH HHS/United States
GR  - P30 HD002274/HD/NICHD NIH HHS/United States
GR  - HD02274/HD/NICHD NIH HHS/United States
GR  - RR024146/RR/NCRR NIH HHS/United States
GR  - UL1 RR024146/RR/NCRR NIH HHS/United States
GR  - P30 HD002274-42S2/HD/NICHD NIH HHS/United States
GR  - HD036071/HD/NICHD NIH HHS/United States
GR  - R01 HD036071-02/HD/NICHD NIH HHS/United States
GR  - R01 HD036071/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120215
PL  - England
TA  - Genes Brain Behav
JT  - Genes, brain, and behavior
JID - 101129617
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (CYFIP2 protein, human)
RN  - 0 (FMR1 protein, human)
RN  - 139135-51-6 (Fragile X Mental Retardation Protein)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*biosynthesis/genetics
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Fragile X Mental Retardation Protein/genetics/metabolism
MH  - Fragile X Syndrome/genetics/*metabolism
MH  - Gene Expression Regulation/physiology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Primary Cell Culture
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/genetics/physiology
MH  - Up-Regulation/*physiology
MH  - Young Adult
PMC - PMC3319643
MID - NIHMS351743
EDAT- 2012/01/25 06:00
MHDA- 2012/09/11 06:00
PMCR- 2013/04/01
CRDT- 2012/01/25 06:00
PHST- 2012/01/25 06:00 [entrez]
PHST- 2012/01/25 06:00 [pubmed]
PHST- 2012/09/11 06:00 [medline]
PHST- 2013/04/01 00:00 [pmc-release]
AID - 10.1111/j.1601-183X.2012.00768.x [doi]
PST - ppublish
SO  - Genes Brain Behav. 2012 Apr;11(3):332-41. doi: 10.1111/j.1601-183X.2012.00768.x. 
      Epub 2012 Feb 15.