Tubulin Regulates Plasma Membrane Ca 2+ -ATPase Activity in a Lipid Environment-dependent Manner

Ca 2+ plays a crucial role in cell signaling, cytosolic Ca 2+ can change up to 10,000-fold in concentration due to the action of Ca 2+ -ATPases, including PMCA, SERCA and SCR. The regulation and balance of these enzymes are essential to maintain cytosolic Ca 2+ homeostasis. Our laboratory has discovered a novel PMCA regulatory system, involving acetylated tubulin alone or in combination with membrane lipids. This regulation controls cytosolic Ca 2+ levels and influences cellular properties such as erythrocyte rheology. This review summarizes the findings on the regulatory mechanism of PMCA activity by acetylated tubulin in combination with lipids. The combination of tubulin cytoskeleton and membrane lipids suggests a novel regulatory system for PMCA, which consequently affects cytosolic Ca 2+ content, depending on cytoskeletal and plasma membrane dynamics. Understanding the interaction between acetylated tubulin, lipids and PMCA activity provides new insights into Ca 2+ signaling and cell function. Further research may shed light on potential therapeutic targets for diseases related to Ca 2+ dysregulation. This discovery contributes to a broader understanding of cellular processes and offers opportunities to develop innovative approaches to treat Ca 2+ -related disorders. By elucidating the complex regulatory mechanisms of Ca 2+ homeostasis, we advance our understanding of cell biology and its implications for human health.