Remodeling of the cardiac striatin interactome and its dynamics in the diabetic heart

Diabetic cardiomyopathy (DbCM) is a silent and complex condition involving numerous signaling pathways that impair cardiomyocyte metabolism and cardiac performance. Striatin (STRN) is a multifaceted protein that binds metabolic proteins, yet its role in diabetic heart remains unexplored. Here we characterized the cardiac STRN interactome by performing immunoprecipitation on left ventricle (LV) proteins from control and diabetic hearts (rats treated with streptozotocin for 24 weeks) to dissect its derivative protein complex. Diabetic rats exhibited pathological heart remodeling characterized by increased heart weight/body weight ratio, elevated levels of Atrial Natriuretic Factor (ANF), and altered expression of alpha and beta-myosin heavy chain isoforms. Notably, STRN expression mirrored that of the remodeling marker ANF across all cardiac chambers. Proteomic analysis yielded 247 proteins interacting with STRN exclusively in diabetic LV, 94 in both control and diabetic LV, and 11 only in control LV. STRN retained a higher interaction with some STRN interacting phosphatase and kinase complex (STRIPAK) proteins (i.e. protein phosphatase 2A (PP2A), and sarcolemmal associated membrane protein (SLMAP)) in diabetic LV, indicating a preserved role of this signalosome in diabetic settings. Functional enrichment and gene ontology revealed that the STRN interactome in diabetic LV carried signalosomes related to cardiac contractility, endoplasmic reticulum stress, mitochondrial function, and apoptotic processes. Western blot experiments confirmed the interaction between STRN and SLMAP in both control and diabetic heart. These data suggest a pivotal role for the STRN signalosome in cardiometabolic disorders, potentially paving the way for novel therapeutic management of DbCM. Targeting the STRN interactome in DbCM, mainly the first-line interactors SLMAP, PP2A, and Cav-1 may offer hope for patients with diabetes-induced cardiac injuries.