Roles for the VCP co-factors Npl4 and Ufd1 in neuronal function in Drosophila melanogaster

a.
UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland
b.
UCD School of Biology and Environmental Science, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland
c.
Cell Biology Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA

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Corresponding author: E-mail address: niamh.osullivan@ucd.ie (Niamh C. O'Sullivan)

Current address: Centre for Integrative Physiology, The Hugh Robson Building, The University of Edinburgh, George Square, Edinburgh, EH8 9XD, UK.

摘要

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Abstract: The VCP-Ufd1-Npl4 complex regulates proteasomal processing within cells by delivering ubiquitinated proteins to the proteasome for degradation. Mutations in VCP are associated with two neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) and inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD), and extensive study has revealed crucial functions of VCP within neurons. By contrast, little is known about the functions of Npl4 or Ufd1in vivo. Using neuronal-specific knockdown of Npl4 or Ufd1 in Drosophila melanogaster, we infer that Npl4 contributes to microtubule organization within developing motor neurons. Moreover, Npl4 RNAi flies present with neurodegenerative phenotypes including progressive locomotor deficits, reduced lifespan and increased accumulation of TAR DNA-binding protein-43 homolog (TBPH). Knockdown, but not overexpression, of TBPH also exacerbates Npl4 RNAi-associated adult-onset neurodegenerative phenotypes. In contrast, we find that neuronal knockdown of Ufd1 has little effect on neuromuscular junction (NMJ) organization, TBPH accumulation or adult behaviour. These findings suggest the differing neuronal functions of Npl4 and Ufd1 in vivo.
- Proteasome /
- TDP-43 accumulation /
- Neurodegeneration
Current address: Centre for Integrative Physiology, The Hugh Robson Building, The University of Edinburgh, George Square, Edinburgh, EH8 9XD, UK.
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doi: 10.1016/j.jgg.2017.06.003

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Roles for the VCP co-factors Npl4 and Ufd1 in neuronal function in Drosophila melanogaster

Corresponding author: E-mail address: niamh.osullivan@ucd.ie (Niamh C. O'Sullivan)

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doi: 10.1016/j.jgg.2017.06.003

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Roles for the VCP co-factors Npl4 and Ufd1 in neuronal function in Drosophila melanogaster

Corresponding author: E-mail address: niamh.osullivan@ucd.ie (Niamh C. O'Sullivan)

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