Cardiac Hypertrophy Changes Compartmentation of cAMP in Non-Raft Membrane Microdomains
Standard
Cardiac Hypertrophy Changes Compartmentation of cAMP in Non-Raft Membrane Microdomains. / Pavlaki, Nikoleta; De Jong, Kirstie A; Geertz, Birgit; Nikolaev, Viacheslav O; Froese, Alexander.
In: CELLS-BASEL, Vol. 10, No. 3, 535, 03.03.2021.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Cardiac Hypertrophy Changes Compartmentation of cAMP in Non-Raft Membrane Microdomains
AU - Pavlaki, Nikoleta
AU - De Jong, Kirstie A
AU - Geertz, Birgit
AU - Nikolaev, Viacheslav O
AU - Froese, Alexander
PY - 2021/3/3
Y1 - 2021/3/3
N2 - 3',5'-Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger which plays critical roles in cardiac function and disease. In adult mouse ventricular myocytes (AMVMs), several distinct functionally relevant microdomains with tightly compartmentalized cAMP signaling have been described. At least two types of microdomains reside in AMVM plasma membrane which are associated with caveolin-rich raft and non-raft sarcolemma, each with distinct cAMP dynamics and their differential regulation by receptors and cAMP degrading enzymes phosphodiesterases (PDEs). However, it is still unclear how cardiac disease such as hypertrophy leading to heart failure affects cAMP signals specifically in the non-raft membrane microdomains. To answer this question, we generated a novel transgenic mouse line expressing a highly sensitive Förster resonance energy transfer (FRET)-based biosensor E1-CAAX targeted to non-lipid raft membrane microdomains of AMVMs and subjected these mice to pressure overload induced cardiac hypertrophy. We could detect specific changes in PDE3-dependent compartmentation of β-adrenergic receptor induced cAMP in non-raft membrane microdomains which were clearly different from those occurring in caveolin-rich sarcolemma. This indicates differential regulation and distinct responses of these membrane microdomains to cardiac remodeling.
AB - 3',5'-Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger which plays critical roles in cardiac function and disease. In adult mouse ventricular myocytes (AMVMs), several distinct functionally relevant microdomains with tightly compartmentalized cAMP signaling have been described. At least two types of microdomains reside in AMVM plasma membrane which are associated with caveolin-rich raft and non-raft sarcolemma, each with distinct cAMP dynamics and their differential regulation by receptors and cAMP degrading enzymes phosphodiesterases (PDEs). However, it is still unclear how cardiac disease such as hypertrophy leading to heart failure affects cAMP signals specifically in the non-raft membrane microdomains. To answer this question, we generated a novel transgenic mouse line expressing a highly sensitive Förster resonance energy transfer (FRET)-based biosensor E1-CAAX targeted to non-lipid raft membrane microdomains of AMVMs and subjected these mice to pressure overload induced cardiac hypertrophy. We could detect specific changes in PDE3-dependent compartmentation of β-adrenergic receptor induced cAMP in non-raft membrane microdomains which were clearly different from those occurring in caveolin-rich sarcolemma. This indicates differential regulation and distinct responses of these membrane microdomains to cardiac remodeling.
U2 - 10.3390/cells10030535
DO - 10.3390/cells10030535
M3 - SCORING: Journal article
C2 - 33802377
VL - 10
JO - CELLS-BASEL
JF - CELLS-BASEL
SN - 2073-4409
IS - 3
M1 - 535
ER -