Dilated cardiomyopathy variant R14del increases phospholamban pentamer stability, blunting dynamic regulation of calcium.

ABSTRACT: The sarco(endo)plasmic reticulum Ca²⁺ ATPase (SERCA) is a membrane transporter that creates and maintains intracellular Ca²⁺ stores. In the heart, SERCA is regulated by an inhibitory interaction with the monomeric form of the transmembrane micropeptide phospholamban (PLB). PLB also forms avid homo-pentamers, and the dynamic exchange of PLB between pentamers and SERCA is an important determinant of cardiac responsiveness to exercise. Here, we investigated two naturally occurring pathogenic variants of PLB: a cysteine substitution of Arg9 (R9C) and an in-frame deletion of Arg14 (R14del). Both variants are associated with dilated cardiomyopathy. We previously showed that the R9C mutation causes disulfide crosslinking and hyperstabilization of pentamers. While the pathoge

SUBMITTER: Cleary SR 

PROVIDER: S-EPMC11791128 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature