Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation.
Local translation of proteins in distal dendrites is thought to support synaptic structural plasticity. We have previously shown that metabotropic glutamate receptor (mGluR1) stimulation initiates a phosphorylation cascade, triggering rapid association of some mRNAs with translation machinery near synapses, and leading to protein synthesis. To determine the identity of these mRNAs, a cDNA library produced from distal nerve processes was used to screen synaptic polyribosome-associated mRNA. We identified mRNA for the fragile X mental retardation protein (FMRP) in these processes by use of synaptic subcellular fractions, termed synaptoneurosomes. We found that this mRNA associates with translational complexes in synaptoneurosomes within 1-2 min after mGluR1 stimulation of this preparation, and we observed increased expression of FMRP after mGluR1 stimulation. In addition, we found that FMRP is associated with polyribosomal complexes in these fractions. In vivo, we observed FMRP immunoreactivity in spines, dendrites, and somata of the developing rat brain, but not in nuclei or axons. We suggest that rapid production of FMRP near synapses in response to activation may be important for normal maturation of synaptic connections.
Weiler
I J
IJ
Department of Psychology, University of Illinois, Urbana-Champaign, IL 61801, USA.
Irwin
S A
SA
Klintsova
A Y
AY
Spencer
C M
CM
Brazelton
A D
AD
Miyashiro
K
K
Comery
T A
TA
Patel
B
B
Eberwine
J
J
Greenough
W T
WT
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016375:Antisense Elements (Genetics); D001921:Brain / Q000254:growth & development / Q000378:metabolism; D018076:DNA, Complementary; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D051860:Fragile X Messenger Ribonucleoprotein 1; D015723:Gene Library; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000502:physiology; D015345:Oligonucleotide Probes; D009928:Organ Specificity; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D012118:Resorcinols / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
D000906:Antibodies; D016375:Antisense Elements (Genetics); D018076:DNA, Complementary; D018691:Excitatory Amino Acid Antagonists; D051860:Fragile X Messenger Ribonucleoprotein 1; D005998:Glycine; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C497683:FMR1 protein, human; C096916:FXR1 protein, human; C096915:FXR2 protein, human; C497685:Fmr1 protein, rat; C104077:metabotropic glutamate receptor type 1; C079215:3,5-dihydroxyphenylglycine