Hyperosmotic stress triggers TPM4 phase separation, which recruits glycolytic enzymes to actin filaments to upregulate glycolysis and facilitate actin reorganization.
TPM4 undergoes phase separation under hyperosmotic stress to recruit glycolytic enzymes, providing localized energy for actin cytoskeleton reorganization.
Actin homeostasis is fundamental for cell structure and consumes a large portion of cellular ATP. It has been documented in the literature that certain glycolytic enzymes can interact with actin, indicating an intricate interplay between the cytoskeleton and cellular metabolism. Here we report that hyperosmotic stress triggers actin severing and subsequent phase separation of the actin-binding protein tropomyosin 4 (TPM4). TPM4 condensates recruit glycolytic enzymes such as HK2, PFKM, and PKM2, while wetting actin filaments. Notably, the condensates of TPM4 and glycolytic enzymes are enriched of NADH and ATP, suggestive of their functional importance in cell metabolism. At cellular level, actin filament assembly is enhanced upon hyperosmotic stress and TPM4 condensation, while depletion of TPM4 impairs osmolarity-induced actin reorganization. At tissue level, colocalized condensates of TPM4 and glycolytic enzymes are observed in renal tissues subjected to hyperosmotic stress. Together, our findings suggest that stress-induced actin perturbation may act on TPM4 to organize glycolytic hubs that tether energy production to cytoskeletal reorganization.
Yang et al. (Tue,) conducted a other in Hyperosmotic stress. Hyperosmotic stress (sorbitol) vs. Isosmotic medium was evaluated on Actin reorganization and glycolysis. Hyperosmotic stress triggers TPM4 phase separation, which recruits glycolytic enzymes to actin filaments to upregulate glycolysis and facilitate actin reorganization.