論文 - 詳細
| RRC ID | 89677 |
|---|---|
| 著者 | Mao G, Ito S, Ishimura R, Sakamaki JI, Sasaki R, Uemura T, Ishikawa KI, Komatsu-Hirota S, Akamatsu W, Abe M, Waguri S, Bijarnia-Mahay S, Noda NN, Inada T, Komatsu M. |
| タイトル | The UFSP2-ODR4 complex spatially confines and dynamically controls UFM1 deconjugation to safeguard neuronal proteostasis. |
| ジャーナル | Mol Cell |
| Abstract |
The ubiquitin-fold modifier 1 (UFM1) pathway is essential for endoplasmic-reticulum-associated ribosome quality control (ER-RQC) through UFMylation of the 60S ribosomal protein RPL26, but the regulation and physiological significance of UFM1 deconjugation remain poorly understood. Here, we identify the ER-anchored UFSP2-ODR4 complex as a spatially confined deUFMylation module critical for neuronal proteostasis. Structural modeling and biochemical analyses show that ODR4 recruits UFSP2 to the ER, enabling efficient deUFMylation of RPL26. Disruption of the UFSP2-ODR4 interaction causes the accumulation of UFMylated RPL26 and defective ER-RQC. Neural progenitor-specific knockin mice expressing a catalytically inactive UFSP2 mutant exhibit perinatal lethality, microcephaly, and neuronal apoptosis. We also identify a patient with biallelic UFC1 mutations that enhance UFL1 binding and induce hyper-UFMylation of RPL26 in patient-derived neurons. These findings establish spatially confined deUFMylation as a critical mechanism for safeguarding neuronal proteostasis. |
| 公開日 | 2026-7-9 |
| DOI | 10.1016/j.molcel.2026.06.026 |
| PII | S1097-2765(26)00415-6 |
| PMID | 42425078 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 26 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 26.6 |
| リソース情報 | |
| 遺伝子材料 | CSII-CMV-MCS-IRES2-Bsd (RDB04385) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394) |