Genetic landscape of phospholamban cardiomyopathies

Figures

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  FIGURE 1. Schematic figure illustrating the pathway from PLN gene to protein and its localization at the SR membrane. Key factors and modifications involved in each step of the process are indicated. Post-translational modifications occur at lysine 3 (ubiquitination), cysteine 36 (palmitoylation), cysteines 41 and 46 (nitrosylation). GR, glucocorticoid nuclear receptor; TR, thyroid hormone receptor; COP-I, Coat Protein Complex I; ARF, ADP-ribosylation factor; ARFGAP, ADP-ribosylation factor GTPase-activating protein 1.

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  FIGURE 2. Diagrammatic representation of published PLN variants and associated clinical phenotypes. Each circle represents a different published PLN variant in the specific amino acid, and each square a different phenotype. Protein phosphorylation residues and transmembrane domain are indicated in dashed line boxes. PLN cytoplasmic residues 2–18 interact with a cytoplasmic fragment of SERCA2 while residues 20–30 and 31–52 bind to different transmembrane regions of SERCA2 (Kimura et al., 1996; Kimura et al., 1998; MacLennan et al., 1998; Asahi et al., 1999; Asahi et al., 2003; Toyoshima et al., 2003).

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  FIGURE 3. Functional effects of PLN variants. The schematic depicts the PLN and SERCA2 protein complex at SR membrane, where it regulates Ca2+ homeostasis and cardiac function. Alterations mediated by the different PLN variants are shown, based on currently available experimental evidence.