PTPRF is a stress responsive cytoskeletal checkpoint that coordinates metabolic adaptation in hepatocytes and β cells

Recent research has unveiled a crucial pathway that links metabolic stress to actin reorganization in hepatocytes and pancreatic beta cells. This pathway involves transcriptional repression of the receptor protein tyrosine phosphatase PTPRF by spliced XBP1, a major unfolded protein response factor. In liver cells, when subjected to dietary stress, the absence of PTPRF stimulates insulin signaling, boosts mitochondrial respiration, and diminishes steatosis.

Proteomic assessments reveal that PTPRF interacts with proteins responsible for actin polymerization and cell junctions. When PTPRF is absent, liver cells exhibit improved actin filament organization, which shifts metabolism towards oxidative pathways. Similarly, in beta cells, the absence of PTPF enhances actin polymerization and boosts glucose-stimulated insulin secretion, particularly in individuals with obesity.

Overall, these findings position PTPRF as a nutrient-responsive regulator of cytoskeletal remodeling that integrates hepatic metabolism and beta-cell function. This discovery suggests that PTPRF could serve as a therapeutic target to enhance systemic glucose control.