Linker of nucleoskeleton and cytoskeleton complex proteins in cardiomyopathy

Figures

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  Fig. 1. The cardiomyocyte LINC complex: Magnified view of cardiac myocyte nuclei (blue) in the circled region highlighting the nuclear envelope (NE) and linker between nucleoskeleton and cytoskeleton (LINC) complex. The LINC complex forms a continuous network of protein-protein interactions between the nuclear lamins; lamins A/C, B1, B2; and the various cytoskeletons. Inner nuclear membrane (INM) proteins SUN1 and SUN2 form heterotrimeric complexes that interact via their SUN domain with the KASH domain of the Nesprins that reside in the outer nuclear membrane (ONM). The giant isoforms of Nesprins 1 and 2 may directly link the NE to the sarcomere by interacting with the Z-disk (Z) or indirectly through intermediate binding partners(s). Nesprin 2 is reported at A/I junctions in the sarcomere. Nesprin 1α2 interacts with kinesin 1, thereby linking the NE to the microtubule cytoskeleton and Nesprin 3 indirectly links to the desmin intermediate filaments through plectin. Many other proteins are associated with the LINC complex that interact with lamins or SUN proteins including LAP2α, Emerin, MAN1, LEM2, Luma, and LAP1 and have been shown to play important roles in cardiomyocytes.…

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  Fig. 2. Nesprin family members and isoforms reported in cardiomyocytes. Nesprin 1α2 contains an isoform-specific spectrin repeat (pink) followed by 6 other spectrin repeats (red) and a KASH domain (yellow). Nesprin 1 giant contains N-terminal tandem calponin homology (CH) domains (purple) that bind actin, spectrin repeats (orange), and a C-terminal KASH domain. Nesprin 2 giant contains tandem CH domains, abutted to spectrin repeats (orange) and a KASH domain. Nesprin 3α is comprised of an isoform-specific spectrin repeat (green) that binds plectin followed by 7 spectrin repeats (blue) and a KASH domain. Nesprin 3β is organized similarly to Nesprin 3α, but the isoform-specific spectrin repeat found in 3α