A new tale of an old story: obscurin bridges sarcomeres and intercalated discs in cardiomyocytes

Abstract

Obscurins, encoded by the single OBSCN gene, are giant cytoskeletal proteins of vertebrate striated muscles composed of adhesion and signaling motifs. The prototypical obscurin (obscurin‐A; ~720 kDa) intimately surrounds sarcomeres at M‐bands and Z‐disks where it participates in their assembly, stability and integration with other sarcomeric elements. We have identified a novel obscurin isoform (obscurin‐D) resulting from complex differential splicing at the 3′ end of the gene. Using immunofluorescence combined with confocal microscopy, we show that obscurin‐D preferentially concentrates at the intercalated disc (ID) of cardiomyocytes, a unique membrane microdomain that mediates mechanical and electrical coupling between neighboring cells. More importantly, immuno‐electron microscopy further demonstrated that obscurin‐D is present at the transitional zone of the ID. Consistent with this, biochemical assays indicate that obscurin‐D exists in a complex with ID proteins, including N‐cadherin, vinculin and connexin‐43, potentially acting as a linker between the ID and the sarcomeric cytoskeleton. Experiments are currently under way to further examine the roles of obscurin‐D at the ICD.