Dynamic palmitoylation events following T-cell receptor signaling

• Published in: Communications biology Vol. 3; no. 1; p. 368
• Main Authors: Morrison, Eliot, Wegner, Tatjana, Zucchetti, Andres Ernesto, Álvaro-Benito, Miguel, Zheng, Ashley, Kliche, Stefanie, Krause, Eberhard, Brügger, Britta, Hivroz, Claire, Freund, Christian
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 10.07.2020; Nature Publishing Group UK
• Subjects: Acetyltransferase; Acyltransferase; Acyltransferases - metabolism; Animals; Biology; Cell activation; Fluorescent Antibody Technique; Gas Chromatography-Mass Spectrometry; Golgi apparatus; Humans; Insecta; Isoforms; Jurkat Cells - metabolism; Life Sciences; Lipoylation; Lymphocytes T; Palmitic acid; Palmitoylation; R-SNARE Proteins - metabolism; Receptor mechanisms; Receptors, Antigen, T-Cell - metabolism; Signal Transduction; SNAP receptors; T cell receptors
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-020-1063-5

Palmitoylation is the reversible addition of palmitate to cysteine via a thioester linkage. The reversible nature of this modification makes it a prime candidate as a mechanism for regulating signal transduction in T-cell receptor signaling. Following stimulation of the T-cell receptor we find a number of proteins are newly palmitoylated, including those involved in vesicle-mediated transport and Ras signal transduction. Among these stimulation-dependent palmitoylation targets are the v-SNARE VAMP7, important for docking of vesicular LAT during TCR signaling, and the largely undescribed palmitoyl acyltransferase DHHC18 that is expressed in two isoforms in T cells. Using our newly developed On-Plate Palmitoylation Assay (OPPA), we show DHHC18 is capable of palmitoylating VAMP7 at Cys183. Cellular imaging shows that the palmitoylation-deficient protein fails to be retained at the Golgi and to localize to the immune synapse upon T cell activation.