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
Hebin LiuC E Rudd

Abstract

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 SUMO-RanGAP1 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.

References

Mar 31, 1995·The Journal of Biological Chemistry·J K JackmanP R Findell
Mar 29, 1994·Proceedings of the National Academy of Sciences of the United States of America·F R BischoffH Ponstingl
Aug 16, 1996·The Journal of Biological Chemistry·J Bubeck WardenburgP R Findell
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·A J da SilvaC E Rudd
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·J LiuC E Rudd
Jan 15, 2000·The Journal of Biological Chemistry·S C BunnellL J Berg
Feb 9, 2000·The Journal of Experimental Medicine·C M ParryA Alcami
Mar 10, 2001·Immunity·R J GreenwaldA H Sharpe
Jan 17, 2002·Cell·Andrea PichlerFrauke Melchior
Oct 3, 2002·The Journal of Cell Biology·Stephen C BunnellLawrence E Samelson
Jan 30, 2003·Nature Immunology·Martha S JordanGary A Koretzky
Jun 6, 2003·Current Opinion in Cell Biology·B Booth Quimby, Mary Dasso
Mar 14, 2007·The Journal of Experimental Medicine·Vincenzo Di BartoloOreste Acuto
May 12, 2007·Trends in Cell Biology·Hai WuGerald R Crabtree
Dec 21, 2007·European Journal of Immunology·Helga SchneiderChristopher E Rudd
Feb 29, 2008·Molecular Biology of the Cell·Saskia HuttenRalph H Kehlenbach
Sep 2, 2008·Trends in Cell Biology·Hongyan Wang, Christopher E Rudd
Sep 13, 2008·Trends in Cell Biology·Maximiliano A D'Angelo, Martin W Hetzer
Jan 10, 2009·Annual Review of Immunology·Jennifer E Smith-GarvinMartha S Jordan
May 12, 2010·Molecular and Cellular Biology·Juris A GrasisConstantine D Tsoukas
May 13, 2010·Science Signaling·Marco A PurbhooDaniel M Davis
Jun 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hebin LiuChristopher E Rudd
Aug 21, 2010·Nature Reviews. Immunology·Martin R Müller, Anjana Rao
Mar 30, 2011·The Journal of Cell Biology·Nikolaj ZulegerEric C Schirmer
Apr 19, 2011·Annual Review of Biochemistry·André HoelzGünter Blobel
Jun 7, 2011·Nature Immunology·David J WilliamsonKatharina Gaus
Jul 21, 2011·Nature Immunology·Ranjan Sen
Apr 3, 2012·Molecular Cell·Andreas WernerFrauke Melchior
May 5, 2012·Nucleus·Guillaume Chatel, Birthe Fahrenkrog

❮ Previous
Next ❯

Citations

Nov 2, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yiwei XiongHebin Liu
Oct 17, 2018·Frontiers in Immunology·Annemarie van NieuwenhuijzeAdrian Liston
Nov 12, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yiwei XiongHebin Liu
Dec 17, 2020·Development·Valeria GuglielmiMaximiliano A D'Angelo
Apr 2, 2021·Frontiers in Cell and Developmental Biology·Christopher E Rudd
May 2, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Enas HallumiDeborah Yablonski

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPase
fluorescence microscopy
transmission electron microscopy
nuclear translocation
transfection
confocal microscopy
Precipitation
Assay

Software Mentioned

FlowJo
MaxQuant
Mascot
ImageJ
exactive

Related Concepts

Related Feeds

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.