Fragile X mental retardation protein shifts between polyribosomes and stress granules after neuronal injury by arsenite stress or in vivo hippocampal electrode insertion.
Fragile X mental retardation protein (FMRP), the lack of which causes fragile X syndrome, is an RNA-binding protein encoded by the FMR1 gene. FMRP accompanies mRNAs from the nucleus to dendritic regions and is thought to regulate their translation at synapses. It has been shown that FMRP moves into nontranslating stress granules (SGs) during heat stress of cultured fibroblasts (Mazroui et al., 2002). We used a novel method to isolate SGs from neurons by virtue of their TIA-1 (T-cell intracellular antigen 1) protein component, and found that FMRP moved out of polyribosomes and into SGs subsequent to oxidative stress. We then examined FMRP changes in subcellular localization resulting from mechanically induced neuronal injury by placement of electrodes into the dentate gyrus and the perforant path of the hippocampus in vivo. During the first 10 min after electrode insertion into one hippocampus, FMRP shifted into SGs and away from polyribosomes, in both hippocampi. Although the injury discharge subsided beyond 10 s, FMRP levels in polyribosomes and stress granules did not return to basal levels until 30 min after electrode penetration. Our findings suggest that procedures for in vivo induction of long-term potentiation or long-term depression should incorporate a 30 min rest period after electrode insertion, and indicate that the contralateral hippocampus cannot be considered an unstimulated control tissue.
Kim
Soong Ho
SH
Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. kanai@uiuc.edu
Dong
Willie K
WK
Weiler
Ivan Jeanne
IJ
Greenough
William T
WT
D000818:Animals; D018053:Arsenites; D015153:Blotting, Western / Q000379:methods; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004566:Electrodes / Q000009:adverse effects*; D005071:Evoked Potentials / Q000528:radiation effects; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism*; D007839:Functional Laterality; D006624:Hippocampus / Q000473:pathology; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D011132:Polyribosomes / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013312:Stress, Physiological / Q000139:chemically induced / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
D018053:Arsenites; D051860:Fragile X Messenger Ribonucleoprotein 1; D016601:RNA-Binding Proteins; C489666:Tial1 protein, rat; C015001:arsenite