title: Role of selected mutations in the Q/N rich region of TDP-43 in EGFP-12xQ/N-induced aggregate formation.
abstract: The overview of TDP 43 functions immediately disclose a number of open questions regarding its pathological role. The formation of TDP-43 aggregates is one of the major distinguishing features of TDP-43 proteinopathies, especially in patients affected by Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar degeneration (FTLD). At the moment, however, very little is known regarding the biological processes that underlie TDP-43 aggregation and, most importantly, its potential consequences on cellular metabolism. For these reasons, it is particularly important to further investigate this process in order to gain a better understanding of the pathology and to develop novel therapeutic effectors. In this report, we focus on a series of missense mutations associated with disease in the 342-366 region of this protein to examine their ability to affect RNA splicing regulation and to induce aggregate formation. In particular, aggregate formation was assessed in a novel system capable of inducing TDP-43 aggregation in experimental cell lines and primary neuronal cultures. The results of this analysis showed that the presence of two of these missense mutations in the 342-366 region (G348V and N352S) could differentially affect the levels and appearance of TDP-43 aggregation with respect to the wild-type protein. This article is part of a Special Issue entitled RNA-Binding Proteins.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB) 34012 Trieste, Italy.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Budini
authors.forename: Valentina
authors.initials: V
authors.lastname: Romano
authors.forename: S Eréndira
authors.initials: SE
authors.lastname: Avendaño-Vázquez
authors.forename: Sara
authors.initials: S
authors.lastname: Bembich
authors.forename: Emanuele
authors.initials: E
authors.lastname: Buratti
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Baralle
mesh_terms: D015153:Blotting, Western; D002458:Cell Fractionation; D004268:DNA-Binding Proteins / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005091:Exons / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics / Q000502:physiology*; D020125:Mutation, Missense / Q000235:genetics / Q000502:physiology; D009479:Neuropeptides / Q000737:chemistry; D010957:Plasmids / Q000235:genetics; D012326:RNA Splicing; D034741:RNA, Small Interfering / Q000235:genetics; D057177:TDP-43 Proteinopathies; D046509:Tissue Culture Techniques; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D009479:Neuropeptides; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins