Mst4, a novel cardiac STRIPAK complex–associated kinase, regulates cardiomyocyte growth and survival and is upregulated in human cardiomyopathy

• DOI: 10.1016/j.jbc.2024.107255
• Publication Date: 2024-04-04T00:26:47Z
• Authors: Matthias Eden; Marius Leye; Justus Hahn; Emanuel Heilein; Marcin Luzarowski; Bill Völschow; Christin Tannert; Samuel Sossalla; Carlota Lucena-Po...; Derk Frank; Norbert Frey
• Keywords: Sarcolemma

Myocardial failure is associated with adverse remodeling which includes apoptotic loss of cardiomyocytes, hypertrophy as well alterations in cell-cell contacts. Striatin-interacting phosphatase and kinase (STRIPAK) complexes their Mst4 have been linked to the development different diseases. The role targets cardiomyocytes not investigated, yet.Multi tissue immunoblot experiments show highly enriched Mst4-expression rodent hearts. Analyses human biopsy samples from patients suffering dilated cardiomyopathy revealed that upregulated (5,8-fold p<0.001) compared non-failing controls. Increased abundance could also be detected mouse models cardiomyopathy. We confirmed interacts STRIPAK components neonatal rat ventricular indicating present heart. Immunofluorescence stainings molecular interaction studies localized intercalated disc several proteins. Overexpression results In adult Mst4-overexpression increases cellular sarcomeric fractional shortening (p<0.05), enhanced contractility. inhibits cell death shown by reduction cleaved Caspase3 (-69%, p<0.0001) Caspase7 (-80%, Parp1 (-27%, p<0.001). To elucidate potential targets, we performed phosphoproteomics analyses after overexpression inhibition. target candidates at sarcolemma.ConclusionWe identified a novel cardiac regulates cardiomyocyte growth survival.