{"id":393,"title":"RanGAP1 coordinates the ER-lamina interface to drive de novo nuclear envelope reassembly in mouse embryos","title_zh":"RanGAP1 协同内质网—核纤层界面驱动小鼠胚胎核膜从头组装","url":"https://pubmed.ncbi.nlm.nih.gov/42905836","doi":"10.1126/sciadv.aef7931","pmid":"42905836","journal":"Sci Adv","kind":"paper","lang":"en","published_at":"2026-10-21T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Zhang XJ","Zhou CJ","Song CR","Feng ML","Xue FR","Sun D","Yang Q","Ding K","Jiang ZY","Liang CG"],"primary_topic":"early-embryo","topics":[{"slug":"early-embryo","score":3.0,"hits":["totipotency","two-cell","zygote"]},{"slug":"animal-models","score":2.4,"hits":["mouse embryos"]}],"topic_score":3.0,"preference_score":0.0,"preference_labels":[],"llm_score":84.0,"final_score":92.0,"score_dims":{"novelty":86,"rigor":80,"impact":78,"relevance":82,"translation":62},"recommend_reason":"首次揭示 RanGAP1 以非经典结构机制（ER—核纤层耦联）驱动小鼠胚胎核膜从头组装，敲低即致二细胞期阻滞，对理解胚胎基因组激活前后核结构重塑与早期发育失败机制有较高价值；但属基础机制研究，距 ART 临床转化尚远。","keywords":["RanGAP1","核膜重组装","核纤层","内质网","小鼠早期胚胎","SUMO化"],"selected":1,"story_id":344,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"sci-adv","journal_tier":"cns-sub","journal_if":11.7,"is_mock":false,"summary_zh":"该研究在小鼠早期胚胎中探讨 RanGAP1 在核膜（NE）重新组装中的作用。采用 Trim-Away 技术敲低 RanGAP1 后，胚胎阻滞于二细胞期，并出现核孔复合体丢失、核膜组装失败及异常\"渔网状\"膜结构。机制上，RanGAP1 通过将 Lamin A/C、B1、B2 招募至内质网（ER）并共组装，建立 ER 与核纤层耦联的结构范式；其酸性结构域及 Lys526 位点 SUMO-1 修饰为核孔定位所必需。研究揭示 RanGAP1 通过把核纤层蛋白靶向 ER 来协调核纤层组装，为早期胚胎发育及核膜相关发育疾病提供新见解。","summary":"Nuclear envelope (NE) reassembly is essential for the zygote-to-totipotency transition in mammalian embryos. Beyond its classical roles in nuclear transport and maintenance of the RanGTP gradient, the function of RanGAP1 in embryonic NE reassembly has remained elusive. Here, we show that RanGAP1 localizes to the early embryonic NE, driving reassembly via a distinct structural mechanism. Trim-Away-mediated RanGAP1 depletion causes two-cell stage arrest and severe NE defects, including nuclear pore complex (NPC) loss, failed reassembly, and aberrant \"fishnet\" membrane structures. Mechanistically, RanGAP1 establishes a structural paradigm for endoplasmic reticulum (ER)-lamina coupling by recruiting Lamin A/C, B1, and B2 to the ER for coassembly. The acidic domain and SUMO-1 modification at Lys526 (K526) are essential for the NPC localization of RanGAP1. Thus, RanGAP1 orchestrates nuclear lamina (NL) assembly by targeting lamins to the ER. These findings uncover mechanisms of NE reassembly that are critical for early embryogenesis and provide insights into NE-related developmental disorders.","interpretation_basis":null,"fulltext_status":"ok","interpretation":null,"fulltext":{"available":true,"status":"ok","reason":"已取得 Europe PMC OA 全文","pmcid":"PMC13685959","license":"CC BY-NC","chars":29996,"source":"Europe PMC","fetched_at":"2026-11-08T03:59:42+00:00"}}