Lipid Transporters Beam Signals from Cell Membranes

Abstract

Lipid composition in cellular membranes plays an important role in maintaining the structural integrity of cells and in regulating cellular signaling that controls functions of both membrane-anchored and cytoplasmic proteins. ATP-dependent ABC and P4-ATPase lipid transporters, two integral membrane proteins, are known to contribute to lipid translocation across the lipid bilayers on the cellular membranes. In this review, we will highlight current knowledge about the role of cholesterol and phospholipids of cellular membranes in regulating cell signaling and how lipid transporters participate this process.

Structural Analysis of Cholesterol Binding and Sterol Selectivity by ABCG5/G8

“…Studies on cholesterol redistribution in lipid rafts have suggested a TMD sterol access site in ABCG1 (Fig. 4) [16,28,52]. Theoretically, ABCG1 intakes sterols from enriched lipid microdomains, relocating them towards the surrounding sterol-deprived membranes.…”

“…At the cellular level, ABC lipid transporters have been shown to alter the composition of their local membrane environment. Such revisions may come from the subduing of lipid rafts by redistributing the high cholesterol content towards the surrounding membrane regions [16,28]. Using in vivo and in vitro functional assays, we have previously characterized a loss-of-function (LOF) mutation ABCG5A540F, a conserved residue near a putative sterol-binding site in ABCG5/G8 [25,29].…”

Structural analysis of cholesterol binding and sterol selectivity by ABCG5/G8

“…Studies on cholesterol redistribution in lipid rafts have suggested a TMD sterol access site in ABCG1 (Fig. 4) (Ristovski et al, 2021;Sano et al, 2014Sano et al, , 2007. Theoretically, ABCG1 intakes sterols from enriched lipid microdomains, relocating them towards the surrounding sterol-deprived membranes.…”

“…Right. Comparison of cholesterol docking pose (light blue) with the cholesterol (green) in the cryo-EM structure [28]. (B) Volumes of transmembrane domain (TMD) cavities found in the of ATP-bound ABCG1 (yellow, PDB ID: 7R8E) and ABCG5/G8 (blue) calculated by MOLE2.5.…”

“…At the cellular level, ABC lipid transporters have been shown to alter the composition of their local membrane environment. Such revisions may come from the subduing of lipid rafts by redistributing the high cholesterol content towards the surrounding membrane regions (Ristovski et al, 2021; Sano et al, 2014). Using in vivo and in vitro functional assays, we have previously characterized a loss-of-function (LOF) mutation ABCG5 A540F , a conserved residue near a putative sterol-binding site in ABCG5/G8 (Lee et al, 2016; Xavier et al, 2020).…”