Extended-Synaptotagmin-1 and -2 control T cell signaling and function.
EMBO Rep
; 25(1): 286-303, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-38177911
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.
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1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article