The Calmodulin/Striatin Interaction Is Enhanced in Diabetic Hearts and Defines Novel Signaling Clusters Implicated in...

Diabetic cardiomyopathy (DbCM) impairs cardiac performance through complex mechanisms, which limits effective therapies. We investigated the protein networks of calmodulin (CaM), a striatin (STRN)-binding protein implicated in DbCM, and compared them with the STRN network from the same tissues. Using CaM as bait, we precipitated protein clusters from left ventricles (LVs) of diabetic rat hearts at 8 and 24 weeks post-streptozotocin (post-STZ). Diabetic rats exhibited pathological remodeling, evidenced by increased heart-to-body weight ratio, β-MHC protein, and ANF mRNA expression. Western blotting showed elevated STRN, but not PP2A-A or -C subunits, in chronic stages. Proteomic analysis at 24 weeks revealed 49 differentially interacting proteins (DIPs) with CaM: 18 enhanced and 31 diminished in diabetic LVs. Functional annotation highlighted the recruitment of proteins in metabolic pathways (fatty acid elongation and lipid metabolism) and PPAR signaling, alongside reduced interactions in lipid response, glucocorticoid response, calcium signaling, and amino acid biosynthesis. Comparative analysis of CaM and STRN interactomes converged to 231 proteins implicated mainly in metabolic processes. Out of these, three proteins (Hnrnpm, Acot7, and Gsta3) surfaced as regulators of metabolic, oxidative, and post-transcriptional remodeling. These findings reveal novel functional roles for the CaM/STRN complex in DbCM and identify a shared signaling hub that may guide therapeutic strategies for diabetes-associated cardiac deterioration.