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FRET-based cyclic GMP biosensors measure low cGMP concentrations in cardiomyocytes and neurons

Abstract:
Several FRET (fluorescence resonance energy transfer)-based biosensors for intracellular detection of cyclic nucleotides have been designed in the past decade. However, few such biosensors are available for cGMP, and even fewer that detect low nanomolar cGMP concentrations. Our aim was to develop a FRET-based cGMP biosensor with high affinity for cGMP as a tool for intracellular signaling studies. We used the carboxyl-terminal cyclic nucleotide binding domain of Plasmodium falciparum cGMP-dependent protein kinase (PKG) flanked by different FRET pairs to generate two cGMP biosensors (Yellow PfPKG and Red PfPKG). Here, we report that these cGMP biosensors display high affinity for cGMP (EC50 of 23 ± 3 nM) and detect cGMP produced through soluble guanylyl cyclase and guanylyl cyclase A in stellate ganglion neurons and guanylyl cyclase B in cardiomyocytes. These biosensors are therefore optimal tools for real-time measurements of low concentrations of cGMP in living cells.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s42003-019-0641-x

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Physiology Anatomy & Genetics
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Physiology Anatomy & Genetics
Role:
Author


Publisher:
Springer Nature
Journal:
Communications Biology More from this journal
Volume:
2
Article number:
394
Publication date:
2019-10-29
Acceptance date:
2019-10-02
DOI:
EISSN:
2399-3642
ISSN:
2399-3642
Pmid:
31701023


Language:
English
Keywords:
Pubs id:
1070562
Local pid:
pubs:1070562
Deposit date:
2020-06-02

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