Lipid-Protein Interplay: How the Plant Plasma Membrane H-ATPase Dynamically Interacts with Its Lipid Environment: A Review

The plasma membrane (PM) H+-ATPase is the primary electrogenic proton pump in plants, energising secondary transport systems by generating a proton motive force essential for nutrient uptake, cell expansion, and stress responses. This review synthesizes current knowledge on the dynamic interplay between the PM H+-ATPase and its lipid microenvironment, focusing on three critical regulatory dimensions: (i) the structural and mechanistic basis of proton transport, (ii) the modulation of pump activity by membrane lipids (phospholipids, sphingolipids, and sterols), and (iii) the potential role of membrane lateral heterogeneity in spatially organizing H+-ATPases with their regulatory partners. We highlight how specific lipid-protein interactions governed by anionic phospholipids, sterol-dependent membrane properties, and sphingolipid-mediated trafficking fine-tune H+-ATPase function. Emerging evidence suggests that lipids act not only as modulators of pump activity but also as facilitators of nanodomain formation, enabling efficient coupling with phosphorylation-dependent signaling cascades (e.g., auxin, blue light, and abscisic acid pathways). Critically, we evaluate methodological challenges in studying lipid-protein interactions and propose future directions, including high-resolution structural analyses and in vivo imaging, to resolve controversies surrounding detergent-resistant membranes and functional microdomains. By integrating structural, biochemical, and biophysical insights, this review underscores the PM H+-ATPase as a central hub where lipid dynamics and cellular signaling converge to regulate plant growth and adaptation.