Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Jeong Hyang | - |
dc.contributor.author | Chung, Chang Geon | - |
dc.contributor.author | Park, Sung Soon | - |
dc.contributor.author | Lee, Davin | - |
dc.contributor.author | Kim, Kyung Min | - |
dc.contributor.author | Jeong, Yeonjin | - |
dc.contributor.author | Kim, EunSeon | - |
dc.contributor.author | Cho, JaeHo | - |
dc.contributor.author | Jeon, Yu-Mi | - |
dc.contributor.author | Shen, C-K James | - |
dc.contributor.author | Kim, Hyung-Jun | - |
dc.contributor.author | Hwang, Daehee | - |
dc.contributor.author | Lee, Sung Bae | - |
dc.date.accessioned | 2021-01-22T07:09:55Z | - |
dc.date.available | 2021-01-22T07:09:55Z | - |
dc.date.created | 2021-01-07 | - |
dc.date.issued | 2020-12 | - |
dc.identifier.issn | 2050-084X | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/12681 | - |
dc.description.abstract | Cytoplasmic accumulation of TDP-43 in motor neurons is the most prominent pathological feature in amyotrophic lateral sclerosis (ALS). A feedback cycle between nucleocytoplasmic transport (NCT) defect and TDP-43 aggregation was shown to contribute to accumulation of TDP-43 in the cytoplasm. However, little is known about cellular factors that can control the activity of NCT, thereby affecting TDP-43 accumulation in the cytoplasm. Here, we identified via FRAP and optogenetics cytosolic calcium as a key cellular factor controlling NCT of TDP-43. Dynamic and reversible changes in TDP-43 localization were observed in Drosophila sensory neurons during development. Genetic and immunohistochemical analyses identified the cytosolic calcium-Calpain-A-Importin α3 pathway as a regulatory mechanism underlying NCT of TDP-43. In C9orf72 ALS fly models, upregulation of the pathway activity by increasing cytosolic calcium reduced cytoplasmic accumulation of TDP-43 and mitigated behavioral defects. Together, these results suggest the calcium-Calpain-A-Importin α3 pathway as a potential therapeutic target of ALS. © Park et al. | - |
dc.language | English | - |
dc.publisher | eLife Sciences Publications Ltd | - |
dc.title | Cytosolic calcium regulates cytoplasmic accumulation of TDP-43 through Calpain-A and Importin alpha 3 | - |
dc.type | Article | - |
dc.identifier.doi | 10.7554/eLife.60132 | - |
dc.identifier.scopusid | 2-s2.0-85098820188 | - |
dc.identifier.bibliographicCitation | eLife, v.9, pp.e60132 - 31 | - |
dc.description.isOpenAccess | TRUE | - |
dc.subject.keywordPlus | BINDING PROTEIN 43 | - |
dc.subject.keywordPlus | NUCLEAR IMPORT | - |
dc.subject.keywordPlus | HEXANUCLEOTIDE REPEAT | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | ALS | - |
dc.subject.keywordPlus | SCLEROSIS | - |
dc.subject.keywordPlus | RNA | - |
dc.subject.keywordPlus | LOCALIZATION | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.citation.endPage | 31 | - |
dc.citation.startPage | e60132 | - |
dc.citation.title | eLife | - |
dc.citation.volume | 9 | - |