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Experimental Biology and Medicine... Oct 2019Membrane rafts are heterogeneous and dynamic domains that are characterized by tight packing of lipids. They are enriched in cholesterol, sphingolipids, and certain... (Review)
Review
UNLABELLED
Membrane rafts are heterogeneous and dynamic domains that are characterized by tight packing of lipids. They are enriched in cholesterol, sphingolipids, and certain types of proteins. Among these are various cell signaling proteins, which indicate that rafts play an important role in cell signal transduction pathways, including some involved in cancer development, progression, and invasiveness. Due to their increased cholesterol content, raft domains exhibit lower fluidity than the surrounding membrane. The cell membranes of some solid tumors, such as breast and prostate cancer, contain higher levels of cholesterol, which means larger raft domain can form in those membranes. This may stimulate signaling pathways to promote tumor growth and progression. This review focuses on the known raft-dependent regulatory mechanisms that promote prostate cancer progression.
IMPACT STATEMENT
Prostate cancer remains the most common malignancy and second most frequent cause of cancer-related death in men. Cholesterol levels are usually higher in prostate cancer cells. This affects the cell membrane composition, with cholesterol and sphingolipid-containing raft membrane domains becoming a greater component. In addition to polar lipids, these domains recruit and regulate certain types of protein, including various cell signaling proteins that are critical to cancer cell survival and invasiveness. This suggests that membrane rafts have a regulatory role in tumor progression, making them a potential target in prostate cancer treatment.
Topics: Animals; Caveolae; Cholesterol; Disease Progression; Humans; Male; Membrane Microdomains; Prostatic Neoplasms; Signal Transduction
PubMed: 31573840
DOI: 10.1177/1535370219870771 -
Current Medicinal Chemistry 2013The bulk structure of biological membranes consists of a bilayer of amphipathic lipids. According to the fluid mosaic model proposed by Singer and Nicholson, the... (Review)
Review
The bulk structure of biological membranes consists of a bilayer of amphipathic lipids. According to the fluid mosaic model proposed by Singer and Nicholson, the glycerophospholipid bilayer is a two-dimensional fluid construct that allows the lateral movement of membrane components. Different types of lateral interactions among membrane components can take place, giving rise to multiple levels of lateral order that lead to highly organized structures. Early observations suggested that some of the lipid components of biological membranes may play active roles in the creation of these levels of order. In the late 1980s, a diverse series of experimental findings collectively gave rise to the lipid raft hypothesis. Lipid rafts were originally defined as membrane domains, i.e., ordered structures created as a consequence of the lateral segregation of sphingolipids and differing from the surrounding membrane in their molecular composition and properties. This definition was subsequently modified to introduce the notion that lipid rafts correspond to membrane areas stabilized by the presence of cholesterol within a liquid-ordered phase. During the past two decades, the concept of lipid rafts has become extremely popular among cell biologists, and these structures have been suggested to be involved in a great variety of cellular functions and biological events. During the same period, however, some groups presented experimental evidence that appeared to contradict the basic tenets that underlie the lipid raft concept. The concept is currently being re-defined, with greater consistency regarding the true nature and role of lipid rafts. In this article we will review the concepts, criticisms, and the novel confirmatory findings relating to the lipid raft hypothesis.
Topics: Animals; Humans; Membrane Lipids; Membrane Microdomains; Membrane Proteins; Models, Molecular
PubMed: 23150999
DOI: No ID Found -
Folia Histochemica Et Cytobiologica 2019Biological membranes are organized in various microdomains, one of the best known being called membrane rafts. The major function of these is thought to organize... (Review)
Review
Biological membranes are organized in various microdomains, one of the best known being called membrane rafts. The major function of these is thought to organize signaling partners into functional complexes. An important protein found in membrane raft microdomains of erythroid and other blood cells is MPP1 (membrane palmitoylated protein 1)/p55. MPP1 (p55) belongs to the MAGUK (membrane-associated guanylate kinase homolog) family and it is a major target of palmitoylation in the red blood cells (RBCs) membrane. The well-known function of this protein is to participate in formation of the junctional complex of the erythrocyte mem-brane skeleton. However, its function as a "raft organizer" is not well understood. In this review we focus on recent reports concerning MPP1 participation in membrane rafts organization in erythroid cells, including its role in signal transduction. Currently it is not known whether MPP1 could have a similar role in cell types other than erythroid lineage. We present also preliminary data regarding the expression level of MPP1 gene in several non-erythroid cell lines.
Topics: Blood Proteins; Cell Membrane; Cholesterol; Erythrocytes; Humans; Membrane Fluidity; Membrane Lipids; Membrane Microdomains; Membrane Proteins; Protein Binding
PubMed: 31099889
DOI: 10.5603/FHC.a2019.0007 -
Biochimica Et Biophysica Acta.... Feb 2022Methods for efficient cyclodextrin-induced lipid exchange have been developed in our lab. These make it possible to almost completely replace the lipids in the outer... (Review)
Review
Methods for efficient cyclodextrin-induced lipid exchange have been developed in our lab. These make it possible to almost completely replace the lipids in the outer leaflet of artificial membranes or the plasma membranes of living cells with exogenous lipids. Lipid replacement/substitution allows detailed studies of how lipid composition and asymmetry influence the structure and function of membrane domains and membrane proteins. In this review, we both summarize progress on cyclodextrin exchange in cells, mainly by the use of methyl-alpha cyclodextrin to exchange phospholipids and sphingolipids, and discuss the issues to consider when carrying out lipid exchange experiments upon cells. Issues that impact interpretation of lipid exchange are also discussed. This includes how overly naïve interpretation of how lipid exchange-induced changes in domain formation can impact protein function.
Topics: Lipid Metabolism; Membrane Lipids; Membrane Microdomains; Membrane Proteins; Mutation, Missense; Phospholipids; alpha-Cyclodextrins
PubMed: 34534531
DOI: 10.1016/j.bbamem.2021.183774 -
Progress in Lipid Research Oct 2010Domains in cell membranes are created by lipid-lipid interactions and are referred to as membrane rafts. Reliable isolation methods have been developed which have shown... (Review)
Review
Domains in cell membranes are created by lipid-lipid interactions and are referred to as membrane rafts. Reliable isolation methods have been developed which have shown that rafts from the same membranes have different proteins and can be sub-fractionated by immunoaffinity methods. Analysis of these raft subfractions shows that they are also comprised of different molecular species of lipids. The major lipid classes present are phospholipids, glycosphingolipids and cholesterol. Model studies show that mixtures of phospholipids, particularly sphingomyelin, and cholesterol form liquid-ordered phase with properties intermediate between a gel and fluid phase. This type of liquid-ordered phase dominates theories of domain formation and raft structure in biological membranes. Recently it has been shown that sphingolipids with long (22-26C) N-acyl fatty acids form quasi-crystalline bilayer structures with diacylphospholipids that have well-defined stoichiometries. A two tier heuristic model of membrane raft structure is proposed in which liquid-ordered phase created by a molecular complex between sphingolipids with hydrocarbon chains of approximately equal length and cholesterol acts as a primary staging area for selecting raft proteins. Tailoring of the lipid anchors of raft proteins takes place at this site. Assembly of lipid-anchored proteins on a scaffold of sphingolipids with asymmetric hydrocarbon chains and phospholipids arranged in a quasi-crystalline bilayer structure serves to concentrate and orient the proteins in a manner that couples them functionally within the membrane. Specificity is inherent in the quasi-crystalline lipid structure of liquid-ordered matrices formed by both types of complex into which protein lipid anchors are interpolated. An interaction between the sugar residues of the glycolipids and the raft proteins provides an additional level of specificity that distinguishes one raft from another.
Topics: Animals; Cholesterol; Detergents; Glycosphingolipids; Humans; Membrane Lipids; Membrane Microdomains; Models, Biological; Phospholipids
PubMed: 20478335
DOI: 10.1016/j.plipres.2010.05.002 -
Drug Target Insights 2020Plasma membranes are not the homogeneous bilayers of uniformly distributed lipids but the lipid complex with laterally separated lipid raft membrane domains, which... (Review)
Review
INTRODUCTION
Plasma membranes are not the homogeneous bilayers of uniformly distributed lipids but the lipid complex with laterally separated lipid raft membrane domains, which provide receptor, ion channel and enzyme proteins with a platform. The aim of this article is to review the mechanistic interaction of drugs with membrane lipid rafts and address the question whether drugs induce physicochemical changes in raft-constituting and raft-surrounding membranes.
METHODS
Literature searches of PubMed/MEDLINE and Google Scholar databases from 2000 to 2020 were conducted to include articles published in English in internationally recognized journals. Collected articles were independently reviewed by title, abstract and text for relevance.
RESULTS
The literature search indicated that pharmacologically diverse drugs interact with raft model membranes and cellular membrane lipid rafts. They could physicochemically modify functional protein-localizing membrane lipid rafts and the membranes surrounding such domains, affecting the raft organizational integrity with the resultant exhibition of pharmacological activity. Raft-acting drugs were characterized as ones to decrease membrane fluidity, induce liquid-ordered phase or order plasma membranes, leading to lipid raft formation; and ones to increase membrane fluidity, induce liquid-disordered phase or reduce phase transition temperature, leading to lipid raft disruption.
CONCLUSION
Targeting lipid raft membrane domains would open a new way for drug design and development. Since angiotensin-converting enzyme 2 receptors which are a cell-specific target of and responsible for the cellular entry of novel coronavirus are localized in lipid rafts, agents that specifically disrupt the relevant rafts may be a drug against coronavirus disease 2019.
PubMed: 33510571
DOI: 10.33393/dti.2020.2185 -
Cardiovascular Disease and Medicine 2020Apolipoprotein A-I (apoAI) upregulates ATP-binding cassette transport A1 (ABCA1) in various cell types. ABCA1 has been shown to induce the redistribution of...
Apolipoprotein A-I (apoAI) upregulates ATP-binding cassette transport A1 (ABCA1) in various cell types. ABCA1 has been shown to induce the redistribution of raft-associated proteins and lipids to the non-raft membrane. This report investigated the effect of apoAI on ABCA1 expression and raft cholesterol and protein distribution, as well as the effect of ABCA1 knockdown on apoAI-induced changes in mouse aortic endothelial cells (MAECs). Our data demonstrated that ABCA1 was distributed in both the lipid raft and non-raft membranes and was coimmunoprecipitated with caveolin-1 (CAV1). ApoAI treatment significantly increased the mRNA and protein levels of ABCA1 and reduced the percentage of ABCA1 in the raft membrane. Our data also showed that free cholesterol (FC) and CAV1 were concentrated in the raft-like detergent-resistant membranes (DRMs) under the control conditions. ApoAI treatment did not alter the cellular level of FC and CAV1 significantly but reduced the percentage of FC and CAV1 in the DRMs. Knockdown of ABCA1 attenuated apoAI-induced redistribution of FC and CAV1. The percentage of FC and CAV1 in the DRMs was correlated inversely with the cellular level of ABCA1, suggesting that apoAI induces relocation of CAV1 and FC from the raft to the non-rail membrane via a mechanism involving upregulation of ABCA1.
PubMed: 38784448
DOI: 10.47496/nl.cdm.2020.01.02 -
Current Alzheimer Research Mar 2011Membrane rafts are sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Membrane rafts isolated from post-mortem AD brain are enriched in... (Review)
Review
Membrane rafts are sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Membrane rafts isolated from post-mortem AD brain are enriched in both β-amyloid and phosphorylated tau. Proteolytic processing of APP to generate β-amyloid, the principle component of amyloid plaques, can occur in membrane rafts, implicating them in the pathogenesis of Alzheimer's disease (AD). Secondary to their role in β-amyloid generation, membrane rafts have more recently been implicated in the accumulation, aggregation and degradation of β-amyloid, with evidence supporting a specific role for membrane raft gangliosides in the binding and aggregation of β-amyloid. In addition, membrane domain composition has a direct impact on both the generation of β-amyloid and its subsequent toxic actions and as such is a key target for the development of therapeutic strategies. This mini-review will focus on recent advances in our understanding of the relevance of membrane composition, of both raft and non-raft domains, to AD progression in models and in human disease. We will discuss how manipulation of membrane composition can alter both the proteolytic processing of APP and the subsequent binding and aggregation of β-amyloid peptide.
Topics: Alzheimer Disease; Amino Acid Sequence; Amyloid beta-Peptides; Animals; Cell Membrane; Humans; Lipid Metabolism; Lipids; Membrane Microdomains; Molecular Sequence Data; Neurons
PubMed: 21222605
DOI: 10.2174/156720511795256008 -
The Journal of Physical Chemistry. B Sep 2020Membrane proteins and lipids have the capacity to associate into lateral domains in cell membranes through mutual or collective interactions. Lipid rafts are functional...
Membrane proteins and lipids have the capacity to associate into lateral domains in cell membranes through mutual or collective interactions. Lipid rafts are functional lateral domains that are formed through collective interactions of certain lipids and which can include or exclude proteins. These domains have been implicated in cell signaling and protein trafficking and seem to be of importance for virus-host interactions. We therefore want to investigate if raft and viral membrane proteins present similar structural features, and how these features are distributed throughout viruses. For this purpose, we performed a bioinformatics analysis of raft and viral membrane proteins from available online databases and compared them to nonraft proteins. In general, transmembrane proteins of rafts and viruses had higher proportions of palmitoyl and phosphoryl residues compared to nonraft proteins. They differed in terms of transmembrane domain length and thickness, with viral proteins being generally shorter and having a smaller accessible surface area per residue. Nontransmembrane raft proteins had increased amounts of palmitoyl, prenyl, and phosphoryl moieties while their viral counterparts were largely myristoylated and phosphorylated. Several of these structural determinants such as phosphorylation are new to the raft field and are extensively discussed in terms of raft functionality and phase separation. Surprisingly, the proportion of palmitoylated viral transmembrane proteins was inversely correlated to the virus size which indicated the implication of palmitoylation in virus membrane curvature and possibly budding. The current results provide new insights into the raft-virus interplay and unveil possible targets for antiviral compounds.
Topics: Cell Membrane; Humans; Lipids; Lipoylation; Membrane Microdomains; Membrane Proteins; Viral Proteins
PubMed: 32813532
DOI: 10.1021/acs.jpcb.0c03435 -
Biochimica Et Biophysica Acta Dec 2005The special physical and functional properties ascribed to lipid rafts in biological membranes reflect their distinctive organization and composition, properties that... (Review)
Review
The special physical and functional properties ascribed to lipid rafts in biological membranes reflect their distinctive organization and composition, properties that are hypothesized to rest in part on the differential partitioning of various membrane components between liquid-ordered and liquid-disordered lipid environments. This review describes the principles and findings of recently developed methods to monitor the partitioning of membrane proteins and lipids between liquid-ordered and liquid-disordered domains in model membranes, and how these approaches can aid in elucidating the properties of rafts in biological membranes.
Topics: Cell Membrane; Lipid Bilayers; Membrane Lipids; Membrane Microdomains; Membrane Proteins; Models, Biological; Phase Transition
PubMed: 16271405
DOI: 10.1016/j.bbamcr.2005.09.003