title: RNA protein granules modulate tau isoform expression and induce neuronal sprouting.
abstract: The neuronal microtubule-associated protein Tau is expressed in different variants, and changes in Tau isoform composition occur during development and disease. Here, we investigate a potential role of the multivalent tau mRNA-binding proteins G3BP1 and IMP1 in regulating neuronal tau expression. We demonstrate that G3BP1 and IMP1 expression induces the formation of structures, which qualify as neuronal ribonucleoprotein (RNP) granules and concentrate multivalent proteins and mRNA. We show that RNP granule formation leads to a >30-fold increase in the ratio of high molecular weight to low molecular weight tau mRNA and an ∼12-fold increase in high molecular weight to low molecular weight Tau protein. We report that RNP granule formation is associated with increased neurite formation and enhanced process growth. G3BP1 deletion constructs that do not induce granule formation are also deficient in inducing neuronal sprouting or changing the expression pattern of tau. The data indicate that granule formation driven by multivalent proteins modulates tau isoform expression and suggest a morphoregulatory function of RNP granules during health and disease.
authors.affiliation: From the Departments of Neurobiology and.
authors.forename: Katharina
authors.initials: K
authors.lastname: Moschner
authors.affiliation: From the Departments of Neurobiology and.
authors.forename: Frederik
authors.initials: F
authors.lastname: Sündermann
authors.affiliation: Zoology, University of Osnabrück, 49076 Osnabrück, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Meyer
authors.affiliation: From the Departments of Neurobiology and.
authors.forename: Abel Pereira
authors.initials: AP
authors.lastname: da Graca
authors.affiliation: From the Departments of Neurobiology and.
authors.forename: Neele
authors.initials: N
authors.lastname: Appel
authors.affiliation: Zoology, University of Osnabrück, 49076 Osnabrück, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Paululat
authors.affiliation: From the Departments of Neurobiology and.
authors.forename: Lidia
authors.initials: L
authors.lastname: Bakota
authors.affiliation: From the Departments of Neurobiology and brandt@biologie.uni-osnabrueck.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Brandt
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D048708:Cell Growth Processes; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004265:DNA Helicases; D017353:Gene Deletion; D006801:Humans; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D016716:PC12 Cells; D000075223:Poly-ADP-Ribose Binding Proteins; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C406144:IGF2BP1 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D020033:Protein Isoforms; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D016875:tau Proteins; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases
keywords: G3BP1; IMP1; MAPs; Microscopic Imaging; Neurite Outgrowth; RNA Protein Granules; RNA-binding Protein; Tau mRNA; Tauopathies; mRNA
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