The immune adaptor SLP-76 binds to SUMO-RANGAP1 at nuclear pore complex filaments to regulate nuclear import of transcription factors in T-cells
Goldberg, Martin W
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Liu, H., Schneider, H., Recino, A., Richardson, C., Goldberg, M. W., & Rudd, C. (2015). The immune adaptor SLP-76 binds to SUMO-RANGAP1 at nuclear pore complex filaments to regulate nuclear import of transcription factors in T-cells. Molecular Cell, 59 840-849. https://doi.org/10.1016/j.molcel.2015.07.015
While immune cell adaptors regulate proximal T-cell signaling, direct regulation of the nuclear pore complex (NPC) has not been reported. NPC has cytoplasmic filaments composed of RanGAP1 and RanBP2 with the potential to interact with cytoplasmic mediators. Here, we show that the immune cell adaptor SLP-76 binds directly to SUMORanGAP1 of cytoplasmic fibrils of the NPC, and that this interaction is needed for optimal NFATc1 and NF-κB p65 nuclear entry in T-cells. Transmission electron microscopy showed anti-SLP-76 cytoplasmic labeling of the majority of NPCs in anti- CD3 activated T-cells. Further, SUMO-RanGAP1 bound to the N-terminal lysine-56 of SLP-76 where the interaction was needed for optimal RanGAP1-NPC localization and GAP exchange activity. While the SLP-76-RanGAP1 (K56E) mutant had no effect on proximal signaling, it impaired NF-ATc1 and p65/RelA nuclear entry and in vivo responses to OVA peptide. Overall, we have identified SLP-76 as a direct regulator of nuclear pore function in T-cells.
The work was supported by the program grant from Wellcome Trust 092627/Z/10/Z (CER).
Wellcome Trust (092627/Z/10/Z)
External DOI: https://doi.org/10.1016/j.molcel.2015.07.015
This record's URL: https://www.repository.cam.ac.uk/handle/1810/250299
Creative Commons Attribution 4.0 International License
Licence URL: http://creativecommons.org/licenses/by/4.0/
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