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...
Saved in:
Main Author: | |
---|---|
Other Authors: | |
Format: | Thesis-Doctor of Philosophy |
Language: | English |
Published: |
Nanyang Technological University
2020
|
Subjects: | |
Online Access: | https://hdl.handle.net/10356/139649 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
id |
sg-ntu-dr.10356-139649 |
---|---|
record_format |
dspace |
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 |
_version_ |
1759856347623456768 |