1. Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.89
Figure 2 Cardiac cytoskeletal proteins involved in cardiomyocyte contraction
Figure 2 | Cardiac cytoskeletal proteins involved in cardiomyocyte contraction. a | Specialized proteins are involved in contractile function and protein quality control of cardiomyocytes. Sarcomeric proteins are organized in an I-band, which consists mainly of actin filaments, and an A-band consisting of both myosin and actin filaments. The M-line, which forms the centre of the sarcomere, consists of only myosin filaments. Actin filaments are crosslinked at the Z-disc, where they interact with desmin (intermediate filaments), dystrophin, α-actinin, and other actin-binding proteins. The actin filaments also interact with microtubules. The microtubules and desmin filaments provide interactions between the sarcolemma, sarcomeres, and the nucleus, and can also bind to mitochondria and are present at the gap junctions and desmosomes. Contractions are the result of ATP-dependent sliding of actin and myosin filaments. Interactions between the sarcomeric and cytoskeletal proteins and costameres are pivotal for transmission of the force generated by the sarcomere to the sarcolemma and the extracellular matrix via intergrins and dystroglycans, but also in mechanotransduction, which allows cardiomyocytes to sense and respond to mechanical stimuli via activation of cytoskeletal signalling involving integrins and Z-disc proteins. Ion-channel function is modulated by actin-binding proteins, which link the channel to the cytoskeleton. The intercalated discs consist of three main junctional complexes: desmosomes, adherens junctions (fascia adherens in cardiac muscle), and gap junctions. Gap junctions are essential for chemical and electrical coupling of neighbouring cells, whereas desmosomes and adherens junctions constitute the mechanical intercellular junctions in cardiomyocytes. Adherens junctions link the intercalated disc to the actin cytoskeleton, and desmosomes attach to intermediate filaments. b | SR–mitochondrial contacts (SMCs) are places at which crosstalk between the SR and mitochondria occur. Basal Ca2+ oscillations from SR to mitochondria drive mitochondrial metabolism for the production of NADH and ATP. SMCs are present at the microtubules, and disruption by histone deacetylase 6-induced de-acetylation of the microtubules results in altered calcium handling and energy depletion, and consequently structural remodelling, contractile dysfunction, and progression of cardiac disease.
Henning, R. H. & Brundel, B. J. J. M. (2017) Proteostasis in cardiac health and disease
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