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Review
. 2022 Dec 19;23(24):16223.
doi: 10.3390/ijms232416223.

Cardiac Sarcomere Signaling in Health and Disease

Ashley A Martin  1 , Brian R Thompson  1 , Dongwoo Hahn  1 , Addeli Bez Batti Angulski  1 , Nora Hosny  1 , Houda Cohen  1 , Joseph M Metzger  1
Affiliations
Review

Cardiac Sarcomere Signaling in Health and Disease

Ashley A Martin et al. Int J Mol Sci. .

Abstract

The cardiac sarcomere is a triumph of biological evolution wherein myriad contractile and regulatory proteins assemble into a quasi-crystalline lattice to serve as the central point upon which cardiac muscle contraction occurs. This review focuses on the many signaling components and mechanisms of regulation that impact cardiac sarcomere function. We highlight the roles of the thick and thin filament, both as necessary structural and regulatory building blocks of the sarcomere as well as targets of functionally impactful modifications. Currently, a new focus emerging in the field is inter-myofilament signaling, and we discuss here the important mediators of this mechanism, including myosin-binding protein C and titin. As the understanding of sarcomere signaling advances, so do the methods with which it is studied. This is reviewed here through discussion of recent live muscle systems in which the sarcomere can be studied under intact, physiologically relevant conditions.

Keywords: cardiac muscle; heart disease; myosin; myosin-binding protein c; sarcomere; titin; troponin.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Illustration of the Cardiac Muscle Sarcomere. In this figure, the illustration shows the proteins assembled to construct the cardiac muscle sarcomere.
Figure 2
Figure 2
Inter-myofilament Signaling in the Cardiac Sarcomere. This figure depicts regulation of thin filament activation, which is driven through calcium binding to troponin C (TnC), TnC and troponin I (TnI) interactions, and the position of tropomyosin (Tm). It also illustrates activation of the thick filament regulated through myosin head states. Myosin-binding protein C has also been included due to its role in regulating interactions between the thin and thick filament.
Figure 3
Figure 3
Function of the Cardiac-Expressed Sarcometer. This model illustrates the construction of the cardiac TnC biosensor which functions through changes in FRET fluorescence driven by the conformational changes TnC undergoes in response to calcium binding, TnC-TnI interactions, myosin cycling, the activation states of myosin, and changes in load. This biosensor has been expressed in a stable transgenic mouse line and can be used to study sarcomere activation in isolated, intact cardiac myocytes and intact cardiac papillary muscles.
See this image and copyright information in PMC

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