Reference - Detail
| RRC ID | 83631 |
|---|---|
| Author | Men Y, Hirayama S, Ao S, Sakurai Y, Shibata Y, Lo M, Sato Y, Murata S. |
| Title | ESCRT-I and PTPN23 mediate microautophagy of ubiquitylated tau aggregates. |
| Journal | J Cell Biol |
| Abstract |
Protein aggregates are degraded by both the autophagy-lysosomal and the ubiquitin-proteasome pathways. Macroautophagy and microautophagy, two forms of the autophagy-lysosomal pathway, are widely conserved across eukaryotes. While macroautophagy has been extensively studied in the context of degradation of protein aggregates, microautophagy remains less explored. Here, we identify the UBAP1-containing ESCRT-I complex and PTPN23 as new regulators for degradation of aggregated proteins through an unbiased genome-wide CRISPR knockout screen, using a cell line expressing tau repeat domain (tauRD) aggregates. ESCRT-I recognizes ubiquitylated tauRD via the UEV domain of TSG101. The accessory protein PTPN23, instead of ESCRT-II, bridges ESCRT-I and ESCRT-III to complete the endosomal microautophagy of ubiquitylated tauRD aggregates. Our results uncover the molecular mechanism underlying the degradation of tau aggregates by endosomal microautophagy. |
| Volume | 224(6) |
| Published | 2025-6-2 |
| DOI | 10.1083/jcb.202406120 |
| PII | 277371 |
| PMID | 40197510 |
| PMC | PMC11977513 |
| MeSH | Autophagy* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Endosomal Sorting Complexes Required for Transport* / genetics Endosomal Sorting Complexes Required for Transport* / metabolism Endosomes / metabolism HEK293 Cells HeLa Cells Humans Lysosomes / metabolism Microautophagy* Protein Aggregates Protein Tyrosine Phosphatases, Non-Receptor Proteolysis Transcription Factors / genetics Transcription Factors / metabolism Ubiquitination tau Proteins* / genetics tau Proteins* / metabolism |
| IF | 8.811 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 33 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) |
| DNA material | CSII-EF-MCS (RDB04378) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |