Plasma Membrane Lipids: An Important Binding Site for All Lipoprotein Classes

Markus Axmann,Birgit Plochberger,Mario Mikula,Witta Monika Strobl,Florian Weber,Herbert Stangl

doi:10.3390/membranes11110882

Markus Axmann, Birgit Plochberger + Show 4 more

Open Access

https://doi.org/10.3390/membranes11110882

Copy DOI

Abstract

Cholesterol is one of the main constituents of plasma membranes; thus, its supply is of utmost importance. This review covers the known mechanisms of cholesterol transfer from circulating lipoprotein particles to the plasma membrane, and vice versa. To achieve homeostasis, the human body utilizes cellular de novo synthesis and extracellular transport particles for supply of cholesterol and other lipids via the blood stream. These lipoprotein particles can be classified according to their density: chylomicrons, very low, low, and high-density lipoprotein (VLDL, LDL, and HDL, respectively). They deliver and receive their lipid loads, most importantly cholesterol, to and from cells by several redundant routes. Defects in one of these pathways (e.g., due to mutations in receptors) usually are not immediately fatal. Several redundant pathways, at least temporarily, compensate for the loss of one or more of them, but the defects trigger systemic diseases, such as atherosclerosis later on. Recently, intracellular membrane–membrane contact sites were shown to be involved in intracellular cholesterol transfer and the plasma membrane itself has been proposed to act as a binding site for lipoprotein-mediated cargo unloading.

Highlights

Cholesterol is an essential constituent of cellular membranes [1]
Intracellular membrane–membrane contact sites were shown to be involved in intracellular cholesterol transfer and the plasma membrane itself has been proposed to act as a binding site for lipoprotein-mediated cargo unloading
HDL-derived lipids are removed from the circulation by at least two pathways: an indirect pathway in which CEs from HDL particles are transferred to low-density lipoprotein (LDL) or very low-density lipoprotein (VLDL) particles facilitated by cholesteryl ester transfer protein (CETP) [30], and a direct one via selective lipid uptake by the liver [31], mediated by the selective cholesteryl ester uptake pathway via an integral cell membrane protein named scavenger receptor class B type 1 (SR-B1) [32,33,34]

Summary

Introduction

Cholesterol is an essential constituent of cellular membranes [1]. It is not uniformly allocated among cell compartments and membranes [2], leading to a spatial and temporal concentration gradient between membrane partitions [3]. HDL-derived lipids are removed from the circulation by at least two pathways: an indirect pathway in which CEs from HDL particles are transferred to LDL or VLDL particles facilitated by cholesteryl ester transfer protein (CETP) [30], and a direct one via selective lipid uptake by the liver [31], mediated by the selective cholesteryl ester uptake pathway via an integral cell membrane protein named scavenger receptor class B type 1 (SR-B1) [32,33,34]. It is conceivable that the second “lower affinity binding site”, described by Monty Krieger’s group, is the plasma membrane itself In support of this concept, we have shown that the cholesterol transfer rate to cholesterol-starved cells mainly depends on the cholesterol content of the lipoprotein particle in cell lines overexpressing SR-B1 [53,54]. The lipids of the plasma membrane itself may act as a binding site contributing to transcytosis and possibly functioning as a sort of overflow sink for excess lipoprotein particles

Redundancy of Cholesterol Transfer Pathways

The Role of the Plasma Membrane Lipids for Cholesterol Uptake

Conclusions