cyclic GMP Archives

In her research, Gaia Calamera‘s has used FRET-based biosensors to investigate subcellular signalling of cyclic GMP in cardiomyocytes, with the aim to learn more about its beneficial effects in the cardiovascular system.

MAIN RESULTS:

New FRET biosensors optimally measure low concentrations of cyclic GMP in cardiomyocytes in real-time
Increased cyclic GMP around the sarcoplasmic reticulum reduces contractility and accelerates myocardial relaxation.
Increased cyclic GMP around mitochondria protects cardiomyocytes from apoptosis.

THESIS DEFENCE:

Thesis: Molecular and functional compartmentation of cGMP in the heart
Candidate: Gaia Calamera
Time: October 12, 2020 at 18:15
Place: Online-based solution, due to the covid-19 situation
Link to university website

SUMMARY:

(1/2) New FRET (fluorescence resonance energy transfer)-sensors that can measure localized pools of cyclic GMP in single adult cardiomyocytes were built. The sensors display high affinity for cyclic GMP. Specifically, they detect cyclic GMP synthesized by soluble guanylyl cyclase and guanylyl cyclase A in stellate ganglion neurons, and by guanylyl cyclase B in cardiomyocytes.

(3) Guanylyl cyclase-B increases cyclic GMP levels around the sarcoplasmic reticulum and the contractile compartment of the cardiomyocytes. This leads to reduced contractility and accelerated myocardial relaxation.

(4) Stimulation of both guanylyl cyclase A and B increase cyclic GMP around the outer mitochondrial membrane. This modulates mitocondrial function and protects cardiomyocytes from programmed cell death.

REFERENCES:

(1) Calamera, G., Ulsund, A. H., Manfra, O., Kim, J. J., Kim, C., Levy, F. O., & Andressen, K. W. (2015, December). Construction of novel cGMP FRET-sensors based on PKG from Plasmodium falciparum. In BMC Pharmacology and Toxicology (Vol. 16, No. S1, p. A34). BioMed Central.

(2) Calamera, G., Li, D., Ulsund, A. H., Kim, J. J., Neely, O. C., Moltzau, L. R., Bjørnerem, M., Paterson, D., Kim, C., Levy, F. O., & Andressen, K. W. (2019). FRET-based cyclic GMP biosensors measure low cGMP concentrations in cardiomyocytes and neurons. Communications biology, 2(1), 1-12.