Please use this identifier to cite or link to this item:
https://www.um.edu.mt/library/oar/handle/123456789/51836
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Cacciottolo, Rebecca | - |
dc.contributor.author | Ciantar, Joanna | - |
dc.contributor.author | Lanfranco, Maia | - |
dc.contributor.author | Borg, Rebecca M. | - |
dc.contributor.author | Vassallo, Neville | - |
dc.contributor.author | Bordonné, Rémy | - |
dc.contributor.author | Cauchi, Ruben J. | - |
dc.date.accessioned | 2020-02-26T13:08:32Z | - |
dc.date.available | 2020-02-26T13:08:32Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Cacciottolo, R., Ciantar, J., Lanfranco, M., Borg, R. M., Vassallo, N., Bordonné, R., & Cauchi, R. J. (2019). SMN complex member Gemin3 self-interacts and has a functional relationship with ALS-linked proteins TDP-43, FUS and Sod1. Scientific Reports, 9(1) doi:10.1038/s41598-019-53508-4 | en_GB |
dc.identifier.uri | https://www.um.edu.mt/library/oar/handle/123456789/51836 | - |
dc.description.abstract | The predominant motor neuron disease in infants and adults is spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), respectively. SMA is caused by insufficient levels of the Survival Motor Neuron (SMN) protein, which operates as part of the multiprotein SMN complex that includes the DEAD-box RNA helicase Gemin3/DDX20/DP103. C9orf72, SOD1, TDP-43 and FUS are ranked as the four major genes causing familial ALS. Accumulating evidence has revealed a surprising molecular overlap between SMA and ALS. Here, we ask the question of whether Drosophila can also be exploited to study shared pathogenic pathways. Focusing on motor behaviour, muscle mass and survival, we show that disruption of either TBPH/TDP-43 or Caz/FUS enhance defects associated with Gemin3 loss-of-function. Gemin3-associated neuromuscular junction overgrowth was however suppressed. Sod1 depletion had a modifying effect in late adulthood. We also show that Gemin3 self-interacts and Gem3ΔN, a helicase domain deletion mutant, retains the ability to interact with its wild-type counterpart. Importantly, mutant:wild-type dimers are favoured more than wild-type:wild-type dimers. In addition to reinforcing the link between SMA and ALS, further exploration of mechanistic overlaps is now possible in a genetically tractable model organism. Notably, Gemin3 can be elevated to a candidate for modifying motor neuron degeneration. | en_GB |
dc.description.sponsorship | This work was supported by the University of Malta Research Fund to RJC, and the Malta Council for Science & Technology Internationalisation Partnership Award to RJC. RC was supported by the Erasmus+ programme of the EU. ML was supported by an Endeavour Scholarship (Malta), part-financed by the EU – European Social Fund under Operational Programme II – Cohesion Policy 2014–2020, “Investing in human capital to create more opportunities and promote the well-being of society”. RMB was supported by a Bjorn Formosa Scholarship for Advanced Research into ALS/MND funded by the non-profit organisation, ALS Malta Foundation, facilitated by the Research Trust (RIDT) of the University of Malta. | en_GB |
dc.language.iso | en | en_GB |
dc.publisher | Nature Research | en_GB |
dc.rights | info:eu-repo/semantics/openAccess | en_GB |
dc.subject | Amyotrophic lateral sclerosis | en_GB |
dc.subject | Neuromuscular transmission | en_GB |
dc.subject | Motor neurons -- Diseases | en_GB |
dc.subject | DNA replication | en_GB |
dc.title | SMN complex member Gemin3 self-interacts and has a functional relationship with ALS-linked proteins TDP-43, FUS and Sod1 | en_GB |
dc.type | article | en_GB |
dc.rights.holder | The copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder. | en_GB |
dc.description.reviewed | peer-reviewed | en_GB |
dc.identifier.doi | 10.1038/s41598-019-53508-4 | - |
dc.publication.title | Scientific Reports | en_GB |
Appears in Collections: | Scholarly Works - FacM&SPB |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
s41598-019-53508-4.pdf | 5.07 MB | Adobe PDF | View/Open |
Items in OAR@UM are protected by copyright, with all rights reserved, unless otherwise indicated.