RNA Protein Granules Modulate tau Isoform Expression and Induce Neuronal Sprouting

Autor(en): Moschner, Katharina
Suendermann, Frederik
Meyer, Heiko
da Graca, Abel Pereira
Appel, Neele
Paululat, Achim 
Bakota, Lidia
Brandt, Roland 
Stichwörter: ASSOCIATION; Biochemistry & Molecular Biology; CENTRAL-NERVOUS-SYSTEM; CORTICAL-NEURONS; GENE; KH DOMAINS; LOCALIZATION; MEMBRANE; MESSENGER-RNA; REVEALS; STRESS GRANULES
Erscheinungsdatum: 2014
Herausgeber: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Journal: JOURNAL OF BIOLOGICAL CHEMISTRY
Volumen: 289
Ausgabe: 24
Startseite: 16814
Seitenende: 16825
Zusammenfassung: 
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 similar to 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.
ISSN: 00219258
DOI: 10.1074/jbc.M113.541425

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