Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses.
Fragile X mental retardation is caused by absence of the RNA-binding protein fragile X mental retardation protein (FMRP), encoded by the FMR1 gene. There is increasing evidence that FMRP regulates transport and modulates translation of some mRNAs. We studied neurotransmitter-activated synaptic protein synthesis in fmr1-knockout mice. Synaptoneurosomes from knockout mice did not manifest accelerated polyribosome assembly or protein synthesis as it occurs in wild-type mice upon stimulation of group I metabotropic glutamate receptors. Direct activation of protein kinase C did not compensate in the knockout mouse, indicating that the FMRP-dependent step is further along the signaling pathway. Visual cortices of young knockout mice exhibited a lower proportion of dendritic spine synapses containing polyribosomes than did the cortices of wild-type mice, corroborating this finding in vivo. This deficit in rapid neurotransmitter-controlled local translation of specific proteins may contribute to morphological and functional abnormalities observed in patients with fragile X syndrome.
Weiler
Ivan Jeanne
IJ
Beckman Institute, Neuroscience Program, and Departments of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. i-weiler@uiuc.edu
Spangler
Chad C
CC
Klintsova
Anna Y
AY
Grossman
Aaron W
AW
Kim
Soong Ho
SH
Bertaina-Anglade
Valerie
V
Khaliq
Hooma
H
de Vries
Froukje E
FE
Lambers
Femke A E
FA
Hatia
Fatima
F
Base
Christine K
CK
Greenough
William T
WT
D000818:Animals; D051860:Fragile X Messenger Ribonucleoprotein 1; D017353:Gene Deletion; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology; D012270:Ribosomes / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
D051860:Fragile X Messenger Ribonucleoprotein 1; D005998:Glycine; D008715:Methionine; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D011188:Potassium; D016601:RNA-Binding Proteins; D012118:Resorcinols; C497684:Fmr1 protein, mouse; C079215:3,5-dihydroxyphenylglycine