title: TDP-43 regulates Drosophila neuromuscular junctions growth by modulating Futsch/MAP1B levels and synaptic microtubules organization.
abstract: TDP-43 is an evolutionarily conserved RNA binding protein recently associated with the pathogenesis of different neurological diseases. At the moment, neither its physiological role in vivo nor the mechanisms that may lead to neurodegeneration are well known. Previously, we have shown that TDP-43 mutant flies presented locomotive alterations and structural defects at the neuromuscular junctions. We have now investigated the functional mechanism leading to these phenotypes by screening several factors known to be important for synaptic growth or bouton formation. As a result we found that alterations in the organization of synaptic microtubules correlate with reduced protein levels in the microtubule associated protein futsch/MAP1B. Moreover, we observed that TDP-43 physically interacts with futsch mRNA and that its RNA binding capacity is required to prevent futsch down regulation and synaptic defects.
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Trieste, Italy.
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Godena
authors.forename: Giulia
authors.initials: G
authors.lastname: Romano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Romano
authors.forename: Chiara
authors.initials: C
authors.lastname: Appocher
authors.forename: Raffaella
authors.initials: R
authors.lastname: Klima
authors.forename: Emanuele
authors.initials: E
authors.lastname: Buratti
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Baralle
authors.forename: Fabian
authors.initials: F
authors.lastname: Feiguin
mesh_terms: D000107:Acetylation; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000254:growth & development* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D014404:Tubulin; C409635:futsch protein, Drosophila; C085284:microtubule-associated protein 1B