title: Dendritic localization of the translational repressor Pumilio 2 and its contribution to dendritic stress granules.
abstract: Pumilio (Pum) protein acts as a translational inhibitor in several organisms including yeast, Drosophila, Xenopus, and mammals. Two Pumilio genes, Pum1 and Pum2, have been identified in mammals, but their function in neurons has not been identified. In this study, we found that Pum2 mRNA is expressed during neuronal development and that the protein is found in discrete particles in both the cell body and the dendritic compartment of fully polarized neurons. This finding indicates that Pum2 is a novel candidate of dendritically localized ribonucleoparticles (RNPs). During metabolic stress, Pum2 is present in stress granules (SGs), which are subsequently detected in the somatodendritic domain. It remains excluded from processing bodies under all conditions. When overexpressed in neurons and fibroblasts, Pum2 induces the formation of SGs that also contain T-cell intracellular antigen 1 (TIA-1)-related protein, eukaryotic initiation factor 4E, poly(A)-binding protein, TIA-1, and other RNA-binding proteins including Staufen1 and Barentsz. This induction of SGs is dependent on the RNA-binding domain and a glutamine-rich region in the N terminus of Pum2. This glutamine-rich region behaves in a similar manner as TIA-1 and prion protein, two molecules with known roles in protein aggregation. Pum2 downregulation in neurons via RNA interference (RNAi) interferes with the formation of SGs during metabolic stress. Cotransfection with an RNAi-resistant portion of the Pum2 mRNA restores SG formation. These results suggest a role for Pum2 in dendritic RNPs and SG formation in mammalian neurons.
authors.affiliation: Division of Neural Cell Biology, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: John P
authors.initials: JP
authors.lastname: Vessey
authors.forename: Angelo
authors.initials: A
authors.lastname: Vaccani
authors.forename: Yunli
authors.initials: Y
authors.lastname: Xie
authors.forename: Ralf
authors.initials: R
authors.lastname: Dahm
authors.forename: Daniela
authors.initials: D
authors.lastname: Karra
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kiebler
authors.forename: Paolo
authors.initials: P
authors.lastname: Macchi
mesh_terms: D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D004622:Embryo, Mammalian; D004722:Endoribonucleases / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014404:Tubulin / Q000378:metabolism
chemical_list: D000076122:Disks Large Homolog 4 Protein; D004722:Endoribonucleases; D039561:Eukaryotic Initiation Factor-4E; D051860:Fragile X Messenger Ribonucleoprotein 1; D051528:Guanylate Kinases; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D016708:Synaptophysin; D015534:Trans-Activators; D014404:Tubulin; C501447:Dlg4 protein, mouse; C079240:Mtap2 protein, mouse; C445087:Pum2 protein, mouse; C007293:DAPI; C466279:DCP1A protein, human