The insulin-like growth factor mRNA binding-protein IMP-1 and the Ras-regulatory protein G3BP associate with tau mRNA and HuD protein in differentiated P19 neuronal cells.
Tau mRNA is axonally localized mRNA that is found in developing neurons and targeted by an axonal localization signal (ALS) that is located in the 3'UTR of the message. The tau mRNA is trafficked in an RNA-protein complex (RNP) from the neuronal cell body to the distal parts of the axon, reaching as far as the growth cone. This movement is microtubule-dependent and is observed as granules that contain tau mRNA and additional proteins. A major protein contained in the granule is HuD, an Elav protein family member, which has an identified mRNA binding site on the tau 3'UTR and stabilizes the tau message and several axonally targeted mRNAs. Using GST-HuD fusion protein as bait, we have identified four proteins contained within the tau RNP, in differentiated P19 neuronal cells. In this work, we studied two of the identified proteins, i.e. IGF-II mRNA binding protein 1 (IMP-1), the orthologue of chick beta-actin binding protein-ZBP1, and RAS-GAP SH3 domain binding protein (G3BP). We show that IMP-1 associates with HuD and G3BP-1 proteins in an RNA-dependent manner and binds directly to tau mRNA. We also show an RNA-dependent association between G3BP-1 and HuD proteins. These associations are investigated in relation to the neuronal differentiation of P19 cells.
Atlas
Roee
R
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Behar
Leah
L
Elliott
Evan
E
Ginzburg
Irith
I
D000818:Animals; D030161:Avian Proteins; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004265:DNA Helicases; D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics*
D030161:Avian Proteins; D002352:Carrier Proteins; D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; C498010:ELAVL4 protein, human; C498011:Elavl4 protein, mouse; C406144:IGF2BP1 protein, human; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; C498636:ZBP1 protein, Gallus gallus; D016875:tau Proteins; D004265:DNA Helicases; C116070:G3BP1 protein, human; C492055:G3bp1 protein, mouse; D020365:RNA Helicases