RanGAP1 coordinates the ER-lamina interface to drive de novo nuclear envelope reassembly in mouse embryos
- 1State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia 010070, China.
Abstract
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.
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BibTeX
@article{zhang2026rangap1,
title = {{RanGAP1 coordinates the ER-lamina interface to drive de novo nuclear envelope reassembly in mouse embryos}},
author = {Xiao-Jie Zhang and Cheng-Jie Zhou and Chun-Ru Song and Meng-Lei Feng and Fang-Rui Xue and Dui Sun and Qi Yang and Kang Ding and Zhao-Yu Jiang and Cheng-Guang Liang},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aef7931},
url = {https://www.science.org/doi/10.1126/sciadv.aef7931},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - RanGAP1 coordinates the ER-lamina interface to drive de novo nuclear envelope reassembly in mouse embryos
AU - Xiao-Jie Zhang
AU - Cheng-Jie Zhou
AU - Chun-Ru Song
AU - Meng-Lei Feng
AU - Fang-Rui Xue
AU - Dui Sun
AU - Qi Yang
AU - Kang Ding
AU - Zhao-Yu Jiang
AU - Cheng-Guang Liang
PY - 2026
DA - 2026/10/21
JO - Science Advances
DO - 10.1126/sciadv.aef7931
UR - https://www.science.org/doi/10.1126/sciadv.aef7931
AB - 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.
SN - 2375-2548
ER -