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Distinct submembrane localisation compartmentalises cardiac NPR1 and NPR2 signalling to cGMP

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Distinct submembrane localisation compartmentalises cardiac NPR1 and NPR2 signalling to cGMP. / Subramanian, Hariharan; Froese, Alexander; Jönsson, Peter; Schmidt, Hannes; Gorelik, Julia; Nikolaev, Viacheslav O.

In: NAT COMMUN, Vol. 9, No. 1, 22.06.2018, p. 2446.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Subramanian, H, Froese, A, Jönsson, P, Schmidt, H, Gorelik, J & Nikolaev, VO 2018, 'Distinct submembrane localisation compartmentalises cardiac NPR1 and NPR2 signalling to cGMP', NAT COMMUN, vol. 9, no. 1, pp. 2446. https://doi.org/10.1038/s41467-018-04891-5

APA

Subramanian, H., Froese, A., Jönsson, P., Schmidt, H., Gorelik, J., & Nikolaev, V. O. (2018). Distinct submembrane localisation compartmentalises cardiac NPR1 and NPR2 signalling to cGMP. NAT COMMUN, 9(1), 2446. https://doi.org/10.1038/s41467-018-04891-5

Vancouver

Subramanian H, Froese A, Jönsson P, Schmidt H, Gorelik J, Nikolaev VO. Distinct submembrane localisation compartmentalises cardiac NPR1 and NPR2 signalling to cGMP. NAT COMMUN. 2018 Jun 22;9(1):2446. https://doi.org/10.1038/s41467-018-04891-5

Bibtex

@article{e8abbc9e04584e76865fb157104493e9,
title = "Distinct submembrane localisation compartmentalises cardiac NPR1 and NPR2 signalling to cGMP",
abstract = "Natriuretic peptides (NPs) are important hormones that regulate multiple cellular functions including cardiovascular physiology. In the heart, two natriuretic peptide receptors NPR1 and NPR2 act as membrane guanylyl cyclases to produce 3',5'-cyclic guanosine monophosphate (cGMP). Although both receptors protect from cardiac hypertrophy, their effects on contractility are markedly different, from little effect (NPR1) to pronounced negative inotropic and positive lusitropic responses (NPR2) with unclear underlying mechanisms. Here we use a scanning ion conductance microscopy (SICM) approach combined with F{\"o}rster resonance energy transfer (FRET)-based cGMP biosensors to show that whereas NPR2 is uniformly localised on the cardiomyocyte membrane, functional NPR1 receptors are found exclusively in membrane invaginations called transverse (T)-tubules. This leads to far-reaching CNP/NPR2/cGMP signals, whereas ANP/NPR1/cGMP signals are highly confined to T-tubular microdomains by local pools of phosphodiesterase 2. This provides a previously unrecognised molecular basis for clearly distinct functional effects engaged by different cGMP producing membrane receptors.",
keywords = "Journal Article",
author = "Hariharan Subramanian and Alexander Froese and Peter J{\"o}nsson and Hannes Schmidt and Julia Gorelik and Nikolaev, {Viacheslav O}",
year = "2018",
month = jun,
day = "22",
doi = "10.1038/s41467-018-04891-5",
language = "English",
volume = "9",
pages = "2446",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Distinct submembrane localisation compartmentalises cardiac NPR1 and NPR2 signalling to cGMP

AU - Subramanian, Hariharan

AU - Froese, Alexander

AU - Jönsson, Peter

AU - Schmidt, Hannes

AU - Gorelik, Julia

AU - Nikolaev, Viacheslav O

PY - 2018/6/22

Y1 - 2018/6/22

N2 - Natriuretic peptides (NPs) are important hormones that regulate multiple cellular functions including cardiovascular physiology. In the heart, two natriuretic peptide receptors NPR1 and NPR2 act as membrane guanylyl cyclases to produce 3',5'-cyclic guanosine monophosphate (cGMP). Although both receptors protect from cardiac hypertrophy, their effects on contractility are markedly different, from little effect (NPR1) to pronounced negative inotropic and positive lusitropic responses (NPR2) with unclear underlying mechanisms. Here we use a scanning ion conductance microscopy (SICM) approach combined with Förster resonance energy transfer (FRET)-based cGMP biosensors to show that whereas NPR2 is uniformly localised on the cardiomyocyte membrane, functional NPR1 receptors are found exclusively in membrane invaginations called transverse (T)-tubules. This leads to far-reaching CNP/NPR2/cGMP signals, whereas ANP/NPR1/cGMP signals are highly confined to T-tubular microdomains by local pools of phosphodiesterase 2. This provides a previously unrecognised molecular basis for clearly distinct functional effects engaged by different cGMP producing membrane receptors.

AB - Natriuretic peptides (NPs) are important hormones that regulate multiple cellular functions including cardiovascular physiology. In the heart, two natriuretic peptide receptors NPR1 and NPR2 act as membrane guanylyl cyclases to produce 3',5'-cyclic guanosine monophosphate (cGMP). Although both receptors protect from cardiac hypertrophy, their effects on contractility are markedly different, from little effect (NPR1) to pronounced negative inotropic and positive lusitropic responses (NPR2) with unclear underlying mechanisms. Here we use a scanning ion conductance microscopy (SICM) approach combined with Förster resonance energy transfer (FRET)-based cGMP biosensors to show that whereas NPR2 is uniformly localised on the cardiomyocyte membrane, functional NPR1 receptors are found exclusively in membrane invaginations called transverse (T)-tubules. This leads to far-reaching CNP/NPR2/cGMP signals, whereas ANP/NPR1/cGMP signals are highly confined to T-tubular microdomains by local pools of phosphodiesterase 2. This provides a previously unrecognised molecular basis for clearly distinct functional effects engaged by different cGMP producing membrane receptors.

KW - Journal Article

U2 - 10.1038/s41467-018-04891-5

DO - 10.1038/s41467-018-04891-5

M3 - SCORING: Journal article

C2 - 29934640

VL - 9

SP - 2446

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -