Guanylate binding protein 1-mediated interaction of T cell antigen receptor signaling with the cytoskeleton

The Journal of Immunology : Official Journal of the American Association of Immunologists
Florian ForsterHannes Stockinger

Abstract

GTPases act as important switches in many signaling events in cells. Although small and heterotrimeric G proteins are subjects of intensive studies, little is known about the large IFN-inducible GTPases. In this article, we show that the IFN-γ-inducible guanylate binding protein 1 (GBP-1) is a regulator of T cell activation. Silencing of GBP-1 leads to enhanced activation of early T cell Ag receptor/CD3 signaling molecules, including Lck, that is translated to higher IL-2 production. Mass spectrometry analyses showed that regulatory cytoskeletal proteins, like plastin-2 that bundles actin fibers and spectrin β-chain, brain 1 that links the plasma membrane to the actin cytoskeleton, are binding partners of GBP-1. The spectrin cytoskeleton influences cell spreading and surface expression of TCR/CD3 and the leukocyte phosphatase CD45. We found higher cell spreading and enhanced surface expression of TCR/CD3 and CD45 in GBP-1 silenced T cells that explain their enhanced TCR/CD3 signaling. We conclude that GBP-1 is a downstream processor of IFN-γ via which T cells regulate cytoskeleton-dependent cell functions.

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Citations

Feb 6, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Verena SupperHannes Stockinger
Aug 17, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karin PfistererVladimir Leksa
Mar 3, 2020·Frontiers in Immunology·Alexander T HonkalaSanjay V Malhotra
Jan 6, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Verena SupperHannes Stockinger
Oct 21, 2017·Frontiers in Immunology·Rocío López-PosadasNathalie Britzen-Laurent
Sep 9, 2016·World Journal of Gastroenterology : WJG·Nathalie Britzen-LaurentMichael Stürzl
Dec 19, 2020·Computational and Structural Biotechnology Journal·Francesco CiccareseStefano Indraccolo
Nov 5, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tianle GuYong-Gang Yao

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