The transmembrane peptide DWORF activates SERCA2a via dual mechanisms.

ABSTRACT: The Ca-ATPase isoform 2a (SERCA2a) pumps cytosolic Ca²⁺ into the sarcoplasmic reticulum (SR) of cardiac myocytes, enabling muscle relaxation during diastole. Abnormally high cytosolic [Ca²⁺] is a central factor in heart failure, suggesting that augmentation of SERCA2a Ca²⁺ transport activity could be a promising therapeutic approach. SERCA2a is inhibited by the protein phospholamban (PLB), and a novel transmembrane peptide, dwarf open reading frame (DWORF), is proposed to enhance SR Ca²⁺ uptake and myocyte contractility by displacing PLB from binding to SERCA2a. However, establishing DWORF's precise physiological role requires further investigation. In the present study, we developed cell-based FRET biosensor systems that can report on protein-pr

SUBMITTER: Li A 

PROVIDER: S-EPMC7988493 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature