Functional marriage in plasma membrane: Critical cholesterol level–optimal protein activity
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In physiology, homeostasis refers to the condition where a system exhibits an optimum functional level. In contrast, any variation from this optimum is considered as a dysfunctional or pathological state. In this review, we address the proposal that a critical cholesterol level in the plasma membrane is required for the proper functioning of transmembrane proteins. Thus, membrane cholesterol depletion or enrichment produces a loss or gain of direct cholesterol–protein interaction and/or changes in the physical properties of the plasma membrane, which affect the basal or optimum activity of transmembrane proteins. Whether or not this functional switching is a generalized mechanism exhibited for all transmembrane proteins, or if it works just for an exclusive group of them, is an open question and an attractive subject to explore at a basic, pharmacological and clinical level. © 2020 The British Pharmacological Society
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4 aminobutyric acid A receptor; adenosine triphosphatase (potassium sodium); adenylate cyclase; cholecystokinin A receptor; cholesterol; KV7.2 potassium channel; KV7.3 potassium channel; potassium channel; protein; sodium calcium exchange protein; unclassified drug; calcium cell level; calcium transport; cell membrane; concentration (parameter); enzyme activity; fat content; human; lipid bilayer; molecular docking; molecular dynamics; nonhuman; priority journal; protein expression; protein function; protein lipid interaction; Review; sensitivity analysis; signal transduction; steady state
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