Extended-Synaptotagmin-1 and -2 Control T Cell Signaling and Function

Authors

Nathalia Benavides, Thomas Jefferson UniversityFollow
Claudio G. Giraudo, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

12-19-2023

Comments

This article is the author's final published version in EMBO reports, Volume 25, Issue 1, 12 January 2024, Pg. 286 - 303.

The published version is available at https://doi.org/10.1038/s44319-023-00011-7. Copyright © 2023 The Author(s).

Abstract

Upon T-cell activation, the levels of the secondary messenger diacylglycerol (DAG) at the plasma membrane need to be controlled to ensure appropriate T-cell receptor signaling and T-cell functions. Extended-Synaptotagmins (E-Syts) are a family of inter-organelle lipid transport proteins that bridge the endoplasmic reticulum and the plasma membrane. In this study, we identify a novel regulatory mechanism of DAG-mediated signaling for T-cell effector functions based on E-Syt proteins. We demonstrate that E-Syts downmodulate T-cell receptor signaling, T-cell-mediated cytotoxicity, degranulation, and cytokine production by reducing plasma membrane levels of DAG. Mechanistically, E-Syt2 predominantly modulates DAG levels at the plasma membrane in resting-state T cells, while E-Syt1 and E-Syt2 negatively control T-cell receptor signaling upon stimulation. These results reveal a previously underappreciated role of E-Syts in regulating DAG dynamics in T-cell signaling.

Recommended Citation

Benavides, Nathalia and Giraudo, Claudio G., "Extended-Synaptotagmin-1 and -2 Control T Cell Signaling and Function" (2023). Department of Microbiology and Immunology Faculty Papers. Paper 183.
https://jdc.jefferson.edu/mifp/183

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

38177911

Language

English