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Review
. 2014 Apr 23;114(8):4564-601.
doi: 10.1021/cr400546e. Epub 2014 Mar 3.

Fluorescent sensors for measuring metal ions in living systems

Kyle P Carter  1 , Alexandra M Young, Amy E Palmer
Affiliations
Review

Fluorescent sensors for measuring metal ions in living systems

Kyle P Carter et al. Chem Rev. .
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic of Dexter energy transfer (A), “turn-on” PET (B), and FRET (C).
Figure 2
Figure 2
Diagram of sensors that have been targeted to specific organelles for subcellular metal ion imaging, either with peptide signaling motifs or with chemical groups known to associate with a particular subcellular location. Additionally, probes for which spontaneous accumulation in an organelle has been verified by colocalization studies are shown. More detailed descriptions of particular targeting strategies are discussed in later sections.
Figure 3
Figure 3
Timeline of historical developments in visualizing metal ions in cells.
Figure 4
Figure 4
Quinoline-, fluorescein-, 4-aminonapthalimide-, and BODIPY-based Zn2+ sensors.
Figure 5
Figure 5
The ZP family of Zn2+ sensors.
Figure 6
Figure 6
The ZS, QZ, and ZAP families of Zn2+ sensors.
Figure 7
Figure 7
Rhodamine-, resorufin-, and cyanine-based small-molecule Zn2+ sensors.
Figure 8
Figure 8
Ratiometric small-molecule Zn2+ sensors.
Figure 9
Figure 9
Mechanisms of metal ion sensing by genetically encoded and hybrid probes for Zn2+. (A) The Zap and Zif families consist of one or two Zn2+-finger domains between two FPs. Zn2+ binding induces a conformational change in the Zn2+-finger that leads to a change in FRET ratio. (B) The eCALWY family uses Zn2+ binding domains from Atox1 and WD4. The two FPs associate in the absence of Zn2+, but Zn2+ binding causes association of the binding domains and reduces the FRET efficiency. (C) The hybrid probe CA-FP has an FP linked to CA. When Zn2+ binds to CA, an exogenously added dapoxyl sulfonamide (blue hexagon) can bind to an open site on the Zn2+ ion, leading to a FRET response between the small-molecule fluorophore and the FP.
Figure 10
Figure 10
Heterogeneous distribution of Zn2+ throughout the mammalian cell. Genetically encoded sensors can be targeted to specific compartments with a signaling sequence to selectively monitor the Zn2+ pool of that organelle.
Figure 11
Figure 11
Molecular Cu+ sensors.
Figure 12
Figure 12
Mechanism of metal ion sensing by genetically encoded probes for Cu+. (A) AMT1-FRET, Ace1-FRET, and Mac1-FRET have a cysteine-rich Cu+-binding domain between a CFP/YFP FRET pair such that metal binding results in an increased FRET signal. (B) Cu+ binding to EGFP-Amt1 distorts the β-barrel of EGFP and decreases fluorescence. (C) YFP-Ace1 and related sensors have the Cu+-binding domain of Ace1 inserted between two strands of EYFP. Cu+ binding alters the local environment of the chromophore and leads to an increased fluorescent signal. (D) The eCALWY Zn2+ sensor platform can be tuned for improved selectivity toward Cu+. In the absence of Cu+, association between two FPs produces a FRET signal. CU+-induced association between the metal binding domains of Atox1 and WD4 changes the structure of the sensor and results in a decreased FRET signal.
Figure 13
Figure 13
Calcein (A) and Phen Green SK (B) represent early fluorescent tools for visualizing cellular iron homeostasis.
Figure 14
Figure 14
Small-molecule Fe2+ sensors.
Figure 15
Figure 15
Small-molecule Fe3+ sensors.
Figure 16
Figure 16
Molecular sensors for the biological metals Mn2+, Ni2+, and Co2+.
Figure 17
Figure 17
Molecular sensors for the toxic metals Pb2+, Cd2+, and Hg2+.
Figure 18
Figure 18
Hg2+ sensor built on a spirolactam ring-opening platform.
See this image and copyright information in PMC

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