SpiCee: A Genetic Tool for Subcellular and Cell-Specific Calcium Manipulation

Oriol Ros,1,6 Sarah Baudet,1,6 Yvrick Zagar,1 Karine Loulier,1 Fiona Roche,1 Sandrine Couvet,1 Alain Aghaie,2
Melody Atkins,3 Alice Louail,1 Christine Petit,2,4 Christine Metin,3 Yves Mechulam,5 and Xavier Nicol1,7,*

Abstract

Calcium is a second messenger crucial to a myriad of cellular processes ranging from regulation of metabolism and cell survival to vesicle release and motility. Current strategies to directly manipulate endogenous calcium signals lack cellular and subcellular specificity. We introduce SpiCee, a versatile and genetically encoded chelator combining low- and high-affinity sites for calcium. This scavenger enables altering endogenous calcium signaling and functions in single cells in vitro and in vivo with biochemically controlled subcellular resolution. SpiCee paves the way to investigate local calcium signaling in vivo and directly manipulate
this second messenger for therapeutic use.

Presenter: Ju hee Ryu

Nat Commun. 2023 Apr 29;14(1):2478. doi: 10.1038/s41467-023-38209-x.

Yuanbo Jia ^# 1 2, Jiahui Hu ^# 2 3, Keli An ^1 2, Qiang Zhao ^2 3, Yang Dang ^2 3, Hao Liu ^1 2, Zhao Wei ^1 2, Songmei Geng ⁴, Feng Xu ^5 6

• PMID: 37120459
• PMCID: PMC10148840
• DOI: 10.1038/s41467-023-38209-x

Abstract

Atopic dermatitis (AD) is a chronic skin disease caused by skin immune dyshomeostasis and accompanied by severe pruritus. Although oxidative stress and mechanical scratching can aggravate AD inflammation, treatment targeting scratching is often overlooked, and the efficiency of mechano-chemically synergistic therapy remains unclear. Here, we find that enhanced phosphorylation of focal adhesion kinase (FAK) is associated with scratch-exacerbated AD. We then develop a multifunctional hydrogel dressing that integrates oxidative stress modulation with FAK inhibition to synergistically treat AD. We show that the adhesive, self-healing and antimicrobial hydrogel is suitable for the unique scratching and bacterial environment of AD skin. We demonstrate that it can scavenge intracellular reactive oxygen species and reduce mechanically induced intercellular junction deficiency and inflammation. Furthermore, in mouse AD models with controlled scratching, we find that the hydrogel alleviates AD symptoms, rebuilds the skin barrier, and inhibits inflammation. These results suggest that the hydrogel integrating reactive oxygen species scavenging and FAK inhibition could serve as a promising skin dressing for synergistic AD treatment.