Regulation of T cell receptor signaling by activation-induced zinc influx

Yu, M. et al. (2011) Regulation of T cell receptor signaling by activation-induced zinc influx. Journal of Experimental Medicine, 208(4), pp. 775-785. (doi: 10.1084/jem.20100031)

Abstract

Zinc is a trace element that is essential for innate and adaptive immune responses. In addition to being a structural element of many proteins, zinc also functions as a neurotransmitter and an intracellular messenger. Temporal or spatial changes in bioavailable zinc may influence the activity of several enzymes, including kinases and phosphatases. We provide evidence that zinc functions as an ionic signaling molecule after T cell activation. Cytoplasmic zinc concentrations increased within 1 min after T cell receptor (TCR) triggering, in particular in the subsynaptic compartment. The increase depended on the extracellular zinc concentrations and was inhibited by silencing zinc transporter Zip6. Increased zinc influx reduced the recruitment of SHP-1 to the TCR activation complex, augmented ZAP70 phosphorylation and sustained calcium influx. By calibrating TCR activation thresholds, increased extracellular zinc bioavailability facilitated the induction of T cell proliferative responses to suboptimal stimuli.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Czesnikiewicz-Guzik, Dr Marta
• Authors: Yu, M., Lee, W.-W., Tomar, D., Pryshchep, S., Czesnikiewicz-Guzik, M., Lamar, D.L., Li, G., Singh, K., Tian, L., Weyand, C.M., and Goronzy, J.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: Journal of Experimental Medicine
• Publisher: Rockefeller University Press
• ISSN: 0022-1007
• ISSN (Online): 1540-9538
• Copyright Holders: Copyright © 2011 The Authors
• First Published: First published in Journal of Experimental Medicine 208(4):775-785
• Publisher Policy: Reproduced under a Creative Commons License