Adaptor protein WDFY3 is neuroprotective by counteracting age-dependent decline in proteostasis

Age-dependent decline in proteostasis increases vulnerability of neuronal cells to oxidative stress, altered energy homeostasis and protein aggregation. Recent studies have suggested an adaptor role for BEACH-domain containing proteins (BDCPs) in autophagy-mediated clearance of protein aggregates in...

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Main Author: Fun, Xiu Hui
Other Authors: Guillaume Thibault
Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2020
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Online Access:https://hdl.handle.net/10356/139649
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1396492023-02-28T18:43:46Z Adaptor protein WDFY3 is neuroprotective by counteracting age-dependent decline in proteostasis Fun, Xiu Hui Guillaume Thibault School of Biological Sciences thibault@ntu.edu.sg Science::Biological sciences::Molecular biology Age-dependent decline in proteostasis increases vulnerability of neuronal cells to oxidative stress, altered energy homeostasis and protein aggregation. Recent studies have suggested an adaptor role for BEACH-domain containing proteins (BDCPs) in autophagy-mediated clearance of protein aggregates in neurodegenerative models. Alterations in BDCPs result in protein aggregation and shortened lifespan in Drosophila. However, the exact mechanism by which they regulate autophagy and alleviate neurodegenerative toxicity remains unclear. Here, we report the characterisation of WDFY-3, a BDCP in Caenorhabditis elegans. Like its Drosophila homologue blue cheese, WDFY-3 is widely expressed in the nerve ring and along the entire length of axonal projections, supporting the possibility of having neuron-specific functions. Our results show that wdfy-3 is not required to induce autophagy genetically and at the protein levels in aged HD animals. Additionally, loss of wdfy-3 shortens the lifespan and reduces motility of C. elegans. Surprisingly during aging, there was a reduction in neuronal aggregates in the absence of wdfy-3, suggesting the protective role of WDFY-3 as a stabiliser that sequesters polyglutamine aggregates into inclusion bodies, further reducing toxicity. Together, our data point to the potential role of WDFY-3 in sequestering toxic aggregates upon age-dependent decline in proteostasis. Doctor of Philosophy 2020-05-20T12:18:49Z 2020-05-20T12:18:49Z 2020 Thesis-Doctor of Philosophy Fun, X. H. (2020). Adaptor protein WDFY3 is neuroprotective by counteracting age-dependent decline in proteostasis. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/139649 10.32657/10356/139649 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences::Molecular biology
spellingShingle Science::Biological sciences::Molecular biology
Fun, Xiu Hui
Adaptor protein WDFY3 is neuroprotective by counteracting age-dependent decline in proteostasis
description Age-dependent decline in proteostasis increases vulnerability of neuronal cells to oxidative stress, altered energy homeostasis and protein aggregation. Recent studies have suggested an adaptor role for BEACH-domain containing proteins (BDCPs) in autophagy-mediated clearance of protein aggregates in neurodegenerative models. Alterations in BDCPs result in protein aggregation and shortened lifespan in Drosophila. However, the exact mechanism by which they regulate autophagy and alleviate neurodegenerative toxicity remains unclear. Here, we report the characterisation of WDFY-3, a BDCP in Caenorhabditis elegans. Like its Drosophila homologue blue cheese, WDFY-3 is widely expressed in the nerve ring and along the entire length of axonal projections, supporting the possibility of having neuron-specific functions. Our results show that wdfy-3 is not required to induce autophagy genetically and at the protein levels in aged HD animals. Additionally, loss of wdfy-3 shortens the lifespan and reduces motility of C. elegans. Surprisingly during aging, there was a reduction in neuronal aggregates in the absence of wdfy-3, suggesting the protective role of WDFY-3 as a stabiliser that sequesters polyglutamine aggregates into inclusion bodies, further reducing toxicity. Together, our data point to the potential role of WDFY-3 in sequestering toxic aggregates upon age-dependent decline in proteostasis.
author2 Guillaume Thibault
author_facet Guillaume Thibault
Fun, Xiu Hui
format Thesis-Doctor of Philosophy
author Fun, Xiu Hui
author_sort Fun, Xiu Hui
title Adaptor protein WDFY3 is neuroprotective by counteracting age-dependent decline in proteostasis
title_short Adaptor protein WDFY3 is neuroprotective by counteracting age-dependent decline in proteostasis
title_full Adaptor protein WDFY3 is neuroprotective by counteracting age-dependent decline in proteostasis
title_fullStr Adaptor protein WDFY3 is neuroprotective by counteracting age-dependent decline in proteostasis
title_full_unstemmed Adaptor protein WDFY3 is neuroprotective by counteracting age-dependent decline in proteostasis
title_sort adaptor protein wdfy3 is neuroprotective by counteracting age-dependent decline in proteostasis
publisher Nanyang Technological University
publishDate 2020
url https://hdl.handle.net/10356/139649
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