VPS35 regulates parkin substrate AIMP2 toxicity by facilitating lysosomal clearance of AIMP2
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yun, Seung Pil | - |
dc.contributor.author | Kim, Hyojung | - |
dc.contributor.author | Ham, Sangwoo | - |
dc.contributor.author | Kwon, Seung-Hwan | - |
dc.contributor.author | Lee, Gum Hwa | - |
dc.contributor.author | Shin, Joo-Ho | - |
dc.contributor.author | Lee, Sang Hun | - |
dc.contributor.author | Ko, Han Seok | - |
dc.contributor.author | Lee, Yunjong | - |
dc.date.accessioned | 2021-08-11T15:24:01Z | - |
dc.date.available | 2021-08-11T15:24:01Z | - |
dc.date.issued | 2017-04 | - |
dc.identifier.issn | 2041-4889 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/7667 | - |
dc.description.abstract | Vacuolar protein sorting-associated protein 35 (VPS35) is involved in retrograde transport of proteins from endosomes to trans-Golgi network. Gene mutations in VPS35 are linked to autosomal dominant late-onset Parkinson's disease (PD). Although the identification of VPS35 mutations has provided novel insight about its interactions with several PD-associated genes including leucine-rich repeat kinase 2 (LRRK2) and a-synuclein, little information is available about the molecular mechanisms of cell death downstream of VPS35 dysfunction. In this study, we showed that VPS35 has a role in the lysosomal degradation of parkin substrate aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2), of which accumulation leads to poly (ADP-ribose) polymerase-1 (PARP1)-dependent cell death. VPS35 was co-immunoprecipitated with AIMP2, as well as lysosome-associated membrane protein-2a (Lamp2a). Interestingly, this association was disrupted by PD-associated VPS35 mutant D620N. VPS35 overexpression prevented AIMP2-potentiated cell death and PARP1 activation in SH-SY5Y cells. More importantly, knockdown of VPS35 led to PARP1 activation and cell death, which was AIMP2 dependent. These findings provide new mechanistic insights into the role of VPS35 in the regulation of AIMP2 levels and cell death. As AIMP2 accumulation was reported in PD patient's brains and involved in dopaminergic cell death, identification of VPS35 as a novel regulator of AIMP2 clearance via lysosomal pathway provides alternative venue to control dopaminergic cell death in PD. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Nature Publishing Group | - |
dc.title | VPS35 regulates parkin substrate AIMP2 toxicity by facilitating lysosomal clearance of AIMP2 | - |
dc.type | Article | - |
dc.publisher.location | 영국 | - |
dc.identifier.doi | 10.1038/cddis.2017.157 | - |
dc.identifier.scopusid | 2-s2.0-85037601101 | - |
dc.identifier.wosid | 000401093800014 | - |
dc.identifier.bibliographicCitation | Cell Death and Disease, v.8 | - |
dc.citation.title | Cell Death and Disease | - |
dc.citation.volume | 8 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | CHAPERONE-MEDIATED AUTOPHAGY | - |
dc.subject.keywordPlus | DOPAMINERGIC NEURONAL LOSS | - |
dc.subject.keywordPlus | MITOCHONDRIAL DYSFUNCTION | - |
dc.subject.keywordPlus | RETROMER COMPLEX | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | ALPHA-SYNUCLEIN | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | MUTATION | - |
dc.subject.keywordPlus | NEURODEGENERATION | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordAuthor | VPS35 | - |
dc.subject.keywordAuthor | AIMP2 | - |
dc.subject.keywordAuthor | Parkinson’s disease | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(31538) 22, Soonchunhyang-ro, Asan-si, Chungcheongnam-do, Republic of Korea+82-41-530-1114
COPYRIGHT 2021 by SOONCHUNHYANG UNIVERSITY ALL RIGHTS RESERVED.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.