Phosphatidylinositol 4-Phosphate 5-Kinase β Controls Recruitment of Lipid Rafts into the Immunological Synapse

The Journal of Immunology : Official Journal of the American Association of Immunologists
Marinos KallikourdisAntonella Viola

Abstract

Phosphatidylinositol 4,5-biphosphate (PIP2) is critical for T lymphocyte activation serving as a substrate for the generation of second messengers and the remodeling of actin cytoskeleton necessary for the clustering of lipid rafts, TCR, and costimulatory receptors toward the T:APC interface. Spatiotemporal analysis of PIP2 synthesis in T lymphocytes suggested that distinct isoforms of the main PIP2-generating enzyme, phosphatidylinositol 4-phosphate 5-kinase (PIP5K), play a differential role on the basis of their distinct localization. In this study, we analyze the contribution of PIP5Kβ to T cell activation and show that CD28 induces the recruitment of PIP5Kβ to the immunological synapse, where it regulates filamin A and lipid raft accumulation, as well as T cell activation, in a nonredundant manner. Finally, we found that Vav1 and the C-terminal 83 aa of PIP5Kβ are pivotal for the PIP5Kβ regulatory functions in response to CD28 stimulation.

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Citations

Oct 27, 2016·Nature Reviews. Immunology·Wei WuChenqi Xu
Nov 23, 2017·Frontiers in Immunology·Sara ZumerleAntonella Viola
May 18, 2016·Journal of Cell Science·Chloé GuedjClotilde Randriamampita
Mar 16, 2018·Nature Communications·Nicla PorcielloLoretta Tuosto
Aug 9, 2018·Scientific Reports·Carlos Fernando Odir Rodrigues MeloRodrigo Ramos Catharino
Aug 1, 2019·Cells·Chiara Cassioli, Cosima T Baldari
Jul 25, 2018·Frontiers in Immunology·Loretta Tuosto, Chenqi Xu
Apr 30, 2019·Frontiers in Immunology·Christian M Gawden-Bone, Gillian M Griffiths
Nov 12, 2020·International Journal of Molecular Sciences·Kalpana Mandal
Aug 25, 2018·Biochemical and Biophysical Research Communications·Paul A JanmeyRavi Radhakrishnan

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