The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes

Abstract

Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.

Nanoparticles Coated with Cell Membranes for Biomedical Applications

“…They are responsible for regulating cellular processes such as growth, differentiation, cell apoptosis [ 20 , 21 ] or cytoskeletal reorganization [ 22 ]. It should be noted that many articles demonstrate how cholesterol acts as a modulator of the structural integrity, organization and fluidity of the membrane [ 23 , 24 ].…”

Impact of Plasma Membrane Domains on IgG Fc Receptor Function

“…In recent years, many studies focused on the role of cholesterol in the plasma membrane as a modulator of structural integrity, membrane organization, and fluidity ( 3 , 19 , 20 ). With an amount of up to 40% of all membrane lipids, cholesterol is a major component of mammalian cell membranes ( 21 , 22 ).…”

“…With an amount of up to 40% of all membrane lipids, cholesterol is a major component of mammalian cell membranes ( 21 , 22 ). It consists of a hydrophilic head group linked to a hydrophobic rigid steroid ring system which serves as a spacer between bulky sphingolipids and promotes the formation of distinct dynamic clusters with higher ordering, i.e., lipid rafts ( 3 ).…”

“…Ligand-induced cross-linking of multiple receptors facilitating the recruitment of intracellular signaling components was consequently proposed to be a crucial part of receptor function especially for type I Fc receptors [reviewed in (2)]. Since organized membrane microdomains, i.e., lipid rafts, are known to be enriched for signaling components [summarized in (3)], the question arises to what extent IgG FcR function in immune cells is affected by specified FIGURE 1 | Chemical structure of main lipid classes and composition of cell membranes. The mammalian plasma membrane consists of three lipid classes, namely glycerophospholipids (depicted in blue), sphingolipids (purple), and sterols (yellow) (A).…”

Membrane Rafts: Portals for Viral Entry

“…Rafts may induce conformational changes in resident proteins, affecting their activity ( Sezgin et al, 2017 ). Because of this, lipid rafts are essential for maintenance of cellular functions such as signal transduction ( Koyama-Honda et al, 2020 ), receptor activation ( Shi and Ruan, 2020 ), intracellular lipid and protein trafficking ( Ouweneel et al, 2020 ), spatial organization of the plasma membrane ( van IJzendoorn et al, 2020 ), endocytosis ( Nichols, 2003a ) and extracellular vesicle formation ( Skryabin et al, 2020 ). As a consequence of their broad involvement in cell physiology, lipid rafts play an important role in complex processes including immune response ( Varshney et al, 2016 ), host–pathogen interaction ( Bukrinsky et al, 2020 ), cancer development ( Greenlee et al, 2020 ), and cardiovascular disorders ( Das and Das, 2009 ).…”