Regulation of the Plasma Membrane Calcium ATPases by the actin cytoskeleton

Highlights: • We described a functional interaction between actin and the Plasma Membrane Ca2+-ATPase (PMCA). • Our findings represent a novel regulatory mechanism of the PMCA. • We unveil a new pathway by which the cortical actin cytoskeleton participates in the regulation of cytosolic Ca2+ homeostasis. Associations between the cortical cytoskeleton and the components of the plasma membrane are no longer considered to be merely of structural and mechanical nature but are nowadays recognized as dynamic interactions that modulate a plethora of cellular responses. Reorganization of actin filaments upon diverse stimuli - among which is the rise in cytosolic Ca²⁺ – is involved in cell motility and adhesion, phagocytosis, cytokinesis, and secretion. Actin dynamics also participates in the regulation of ion transport across the membranes where it not only plays a key role in the delivery and stabilization of channels and transporters in the plasma membrane but also in the regulation of their activity. The recently described functional interaction between actin and the Plasma Membrane Ca²⁺-ATPase (PMCA) represents a novel regulatory mechanism of the pump at the time that unveils a new pathway by which the cortical actin cytoskeleton participates in the regulation of cytosolic Ca²⁺ homeostasis. In this review, we summarize the current knowledge on the interaction between the cortical actin cytoskeleton and the PMCA and discuss the possible mechanisms that may explain the pump's modulation.