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A GAPDH serotonylation system couples CD8 + TÂ cell glycolytic metabolism to antitumor immunity.
- Source :
-
Molecular cell [Mol Cell] 2024 Feb 15; Vol. 84 (4), pp. 760-775.e7. Date of Electronic Publication: 2024 Jan 11. - Publication Year :
- 2024
-
Abstract
- Apart from the canonical serotonin (5-hydroxytryptamine [5-HT])-receptor signaling transduction pattern, 5-HT-involved post-translational serotonylation has recently been noted. Here, we report a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) serotonylation system that promotes the glycolytic metabolism and antitumor immune activity of CD8 <superscript>+</superscript> T cells. Tissue transglutaminase 2 (TGM2) transfers 5-HT to GAPDH glutamine 262 and catalyzes the serotonylation reaction. Serotonylation supports the cytoplasmic localization of GAPDH, which induces a glycolytic metabolic shift in CD8 <superscript>+</superscript> T cells and contributes to antitumor immunity. CD8 <superscript>+</superscript> T cells accumulate intracellular 5-HT for serotonylation through both synthesis by tryptophan hydroxylase 1 (TPH1) and uptake from the extracellular compartment via serotonin transporter (SERT). Monoamine oxidase A (MAOA) degrades 5-HT and acts as an intrinsic negative regulator of CD8 <superscript>+</superscript> T cells. The adoptive transfer of 5-HT-producing TPH1-overexpressing chimeric antigen receptor T (CAR-T) cells induced a robust antitumor response. Our findings expand the known range of neuroimmune interaction patterns by providing evidence of receptor-independent serotonylation post-translational modification.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2023 Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 84
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 38215751
- Full Text :
- https://doi.org/10.1016/j.molcel.2023.12.015