In Situ Investigation of Mammalian Inorganic Polyphosphate Localization Using Novel Selective Fluorescent Probes JC-D7 and JC-D8

Inorganic polyphosphate (polyP) is a polymer composed of many orthophosphates linked together by phosphoanhydride bonds. Recent studies demonstrate that in addition to its important role in the function of microorganisms, polyP plays multiple important roles in the pathological and physiological fun...

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Bibliographic Details
Published in:ACS chemical biology 2014-09, Vol.9 (9), p.2101-2110
Main Authors: Angelova, Plamena R, Agrawalla, Bikram Keshari, Elustondo, Pia A, Gordon, Jacob, Shiba, Toshikazu, Abramov, Andrey Y, Chang, Young-Tae, Pavlov, Evgeny V
Format: Article
Language:English
Subjects:
Animals
Astrocytes - metabolism
Benzimidazoles - analysis
Benzimidazoles - chemistry
Benzimidazoles - metabolism
Brain - metabolism
Cells, Cultured
Dimethyl Sulfoxide - chemistry
Disease Models, Animal
Drosophila melanogaster
Fluorescent Dyes - analysis
Fluorescent Dyes - chemistry
Humans
Indoles - analysis
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Lysosomes - metabolism
Mice, Inbred C57BL
Mice, Knockout
Molecular Imaging - methods
Molecular Structure
Naphthalenes - analysis
Naphthalenes - chemistry
Naphthalenes - metabolism
Parkinson Disease - metabolism
Polyphosphates - analysis
Protein Kinases - genetics
Protein-Serine-Threonine Kinases - genetics
Rats
Reproducibility of Results
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Summary:Inorganic polyphosphate (polyP) is a polymer composed of many orthophosphates linked together by phosphoanhydride bonds. Recent studies demonstrate that in addition to its important role in the function of microorganisms, polyP plays multiple important roles in the pathological and physiological function of higher eukaryotes, including mammalians. However, due to the dramatically lower abundance of polyP in mammalian cells when comparing to microorganisms, its investigation poses an experimental challenge. Here, we present the identification of novel fluorescent probes that allow for specific labeling of synthetic polyP in vitro as well as endogenous polyP in living cells. These probes demonstrate high selectivity for the labeling of polyP that was not sensitive to a number of ubiquitous organic polyphosphates, notably RNA. Use of these probes allowed us to demonstrate the real time detection of polyP release from lysosomes in live cells. Furthermore, we have been able to detect the increased levels of polyP in cells with Parkinson’s disease related mutations.
ISSN:1554-8929
1554-8937
DOI:10.1021/cb5000696