Abstract
Essential biochemical reactions and processes within living organisms are coupled to subcellular fluctuations of metal ions. Disturbances in cellular metal ion homeostasis are frequently associated with pathological alterations, including neurotoxicity causing neurodegeneration, as well as metabolic disorders or cancer. Considering these important aspects of the cellular metal ion homeostasis in health and disease, measurements of subcellular ion signals are of broad scientific interest. The investigation of the cellular ion homeostasis using classical biochemical methods is quite difficult, often even not feasible or requires large cell numbers. Here, we report of genetically encoded fluorescent probes that enable the visualization of metal ion dynamics within individual living cells and their organelles with high temporal and spatial resolution. Generally, these probes consist of specific ion binding domains fused to fluorescent protein(s), altering their fluorescent properties upon ion binding. This review focuses on the functionality and potential of these genetically encoded fluorescent tools which enable monitoring (sub)cellular concentrations of alkali metals such as K+, alkaline earth metals including Mg2+ and Ca2+, and transition metals including Cu+/Cu2+ and Zn2+. Moreover, we discuss possible approaches for the development and application of novel metal ion biosensors for Fe2+/Fe3+, Mn2+ and Na+.
Highlights
Vital cells tightly control theircellular ion distributions [1]
These probes were based on a conformational calcium ion
Fe2+ /Fe3+ and Mn2+ probes has been recently proven by Koay et al who modified the specificity of a genetically encoded probe (GEP) by the introduction of mutations in an approved Cu+ sensor, thereby generating probes sensitive for Zn2+ [153]
Summary
Vital cells tightly control their (sub)cellular ion distributions [1]. Alterations of the intracellular ion homeostasis are associated with severe dysfunctions and pathologies. The first successful design of a so-called genetically encoded probe (GEP) was achieved in 1997 boosted our understanding of cell biology as well as molecular and cellular (patho)physiology by Miyawaki et al, who exploited Förster resonance energy transfer (FRET) occurring between a [26,27]. 2+) binding domains [27] These probes were based on a conformational calcium ion The development of this sophisticated probes, referred to as “Cameleons”, opened of GEPs is available, especially for metal ions including protein-based fluorescent sensors for Ca2+ , the door for many further FRET-based indicators that allow real-time recordings of cell signaling. Schematic representationofofthe thefunctional functional principle of genetically encoded probes probes (GEPs). (GEPs)
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