Stephen, L. A., ElMaghloob, Y., McIlwraith, M. J., Yelland, T., Castro Sanchez, P., Roda-Navarro, P. and Ismail, S. (2018) The ciliary machinery is repurposed for T cell immune synapse trafficking of LCK. Developmental Cell, 47(15), 122-132e4. (doi: 10.1016/j.devcel.2018.08.012) (PMID:30220567) (PMCID:PMC6179904)
|
Text
167510.pdf - Published Version Available under License Creative Commons Attribution Non-commercial No Derivatives. 3MB |
Abstract
Upon engagement of the T cell receptor with an antigen-presenting cell, LCK initiates TCR signaling by phosphorylating its activation motifs. However, the mechanism of LCK activation specifically at the immune synapse is a major question. We show that phosphorylation of the LCK activating Y394, despite modestly increasing its catalytic rate, dramatically focuses LCK localization to the immune synapse. We describe a trafficking mechanism whereby UNC119A extracts membrane-bound LCK by sequestering the hydrophobic myristoyl group, followed by release at the target membrane under the control of the ciliary ARL3/ARL13B. The UNC119A N terminus acts as a “regulatory arm” by binding the LCK kinase domain, an interaction inhibited by LCK Y394 phosphorylation, thus together with the ARL3/ARL13B machinery ensuring immune synapse focusing of active LCK. We propose that the ciliary machinery has been repurposed by T cells to generate and maintain polarized segregation of signals such as activated LCK at the immune synapse.
| Item Type: | Articles |
|---|---|
| Additional Information: | CRUK grant number to Beatson A19257. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Elmaghloob, Yasmin Adel Elsayed and Ismail, Dr Shehab |
| Authors: | Stephen, L. A., ElMaghloob, Y., McIlwraith, M. J., Yelland, T., Castro Sanchez, P., Roda-Navarro, P., and Ismail, S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Developmental Cell |
| Publisher: | Elsevier (Cell Press) |
| ISSN: | 1534-5807 |
| ISSN (Online): | 1878-1551 |
| Published Online: | 13 September 2018 |
| Copyright Holders: | Copyright © 2018 The Authors |
| First Published: | First published in Developmental Cell 47:122-132e4 |
| Publisher Policy: | Reproduced under a Creative Commons License |
University Staff: Request a correction | Enlighten Editors: Update this record
Altmetric
Altmetric