Endoplasmic reticulum targeting fluorescent probes to image mobile Zn2+

Fang, Le; Trigiante, Giuseppe; Crespo-Otero, Rachel; Hawes, Chris S.; Philpott, Michael P.; Jones, Christopher R.; Watkinson, Michael

doi:10.1039/C9SC04300D

Endoplasmic reticulum targeting fluorescent probes to image mobile Zn2+

Fang, Le; Trigiante, Giuseppe; Crespo-Otero, Rachel; Hawes, Chris S.; Philpott, Michael P.; Jones, Christopher R.; Watkinson, Michael

Authors

Le Fang

Giuseppe Trigiante

Rachel Crespo-Otero

Chris Hawes c.s.hawes@keele.ac.uk

Michael P. Philpott

Christopher R. Jones

Michael Watkinson

Abstract

Zn2+ plays an important role in the normal function of the endoplasmic reticulum (ER) and its deficiency can cause ER stress, which is related to a wide range of diseases. In order to provide tools to better understand the role of mobile Zn2+ in ER processes, the first custom designed ER-localised fluorescent Zn2+ probes have been developed through the introduction of a cyclohexyl sulfonylurea as an ER-targeting unit with different Zn2+ receptors. Experiments in vitro and in cellulo show that both probes have a good fluorescence switch on response to Zn2+, high selectivity over other cations, low toxicity, ER-specific targeting ability and are efficacious imaging agents for mobile Zn2+ in four different cell lines. Probe 9 has been used to detect mobile Zn2+ changes under ER stress induced by both tunicamycin or thapsigargin, which indicates that the new probes should allow a better understanding of the mechanisms cells use to respond to dysfunction of zinc homeostasis in the ER and its role in the initiation and progression of diseases to be developed.

Journal Article Type	Article
Acceptance Date	Oct 16, 2019
Publication Date	Dec 21, 2019
Journal	Chemical Science
Print ISSN	2041-6520
Publisher	Royal Society of Chemistry
Peer Reviewed	Peer Reviewed
Volume	10
Issue	47
Pages	10881-10887
DOI	https://doi.org/10.1039/C9SC04300D
Publisher URL	http://doi.org/10.1039/C9SC04300D