T cell receptor (TCR) signaling promotes the assembly of RanBP2/RanGAP1-SUMO1/Ubc9 nuclear pore subcomplex via PKC-θ-mediated phosphorylation of RanGAP1
- Sun Yat-Sen University, China
- La Jolla Institute for Immunology, United States
Abstract
The nuclear pore complex (NPC) is the sole and selective gateway for nuclear transport and its dysfunction has been associated with many diseases. The metazoan NPC subcomplex RanBP2, which consists of RanBP2 (Nup358), RanGAP1-SUMO1 and Ubc9, regulates the assembly and function of the NPC. The roles of immune signaling in regulation of NPC remain poorly understood. Here, we show that in human and murine T cells, following TCR stimulation, protein kinase C-θ (PKC-θ) directly phosphorylates RanGAP1 to facilitate RanBP2 subcomplex assembly and nuclear import and, thus, the nuclear translocation of AP-1 transcription factor. Mechanistically, TCR stimulation induces the translocation of activated PKC-θ to the NPC, where it interacts with and phosphorylates RanGAP1 on Ser504 and Ser506. RanGAP1 phosphorylation increases its binding affinity for Ubc9, thereby promoting sumoylation of RanGAP1 and, finally, assembly of the RanBP2 subcomplex. Our findings reveal an unexpected role of PKC-θ as a direct regulator of nuclear import and uncover a phosphorylation-dependent sumoylation of RanGAP1, delineating a novel link between TCR signaling and assembly of the RanBP2 NPC subcomplex.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National Natural Science Foundation of China (31670893)
- Yingqiu Li
National Natural Science Foundation of China (31370886)
- Yingqiu Li
National Natural Science Foundation of China (31170846)
- Yingqiu Li
Guangzhou Science and Technology Project (201904010445)
- Yingqiu Li
Guangdong provincial natural science foundation (2021A1515010543)
- Yingqiu Li
Guangdong Science and Technology Department (2020B1212060031)
- Yingqiu Li
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Juan Carlos Zúñiga-Pflücker, University of Toronto, Sunnybrook Research Institute, Canada
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the Sun Yat-Sen University. All of the animals were handled according to guidelines approved by the Animal Care and Ethics committee of Sun Yat-Sen University. The protocol was approved by the Committee on the Ethics of Animal Experiments of Sun Yat-Sen University (Permit Number: SYSU-IACUC-2019-B616) . The mice were euthanatized by CO2 from compressed gas cylinders, and we complied with all the ethical regulation.
Version history
- Received: February 1, 2021
- Accepted: June 3, 2021
- Accepted Manuscript published: June 10, 2021 (version 1)
- Version of Record published: June 24, 2021 (version 2)
- Version of Record updated: June 28, 2021 (version 3)
Copyright
© 2021, He et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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T cell receptor (TCR) signaling promotes the assembly of RanBP2/RanGAP1-SUMO1/Ubc9 nuclear pore subcomplex via PKC-θ-mediated phosphorylation of RanGAP1
eLife 10:e67123.
https://doi.org/10.7554/eLife.67123
