-
Neurologia 2023Rafts are protein-lipid structural nanodomains involved in efficient signal transduction and the modulation of physiological processes of the cell plasma membrane. Raft... (Review)
Review
INTRODUCTION
Rafts are protein-lipid structural nanodomains involved in efficient signal transduction and the modulation of physiological processes of the cell plasma membrane. Raft disruption in the nervous system has been associated with a wide range of disorders.
DEVELOPMENT
We review the concept of rafts, the nervous system processes in which they are involved, and their role in diseases such as Parkinson's disease, Alzheimer disease, and Huntington disease.
CONCLUSIONS
Based on the available evidence, preservation and/or reconstitution of rafts is a promising treatment strategy for a wide range of neurological disorders.
Topics: Humans; Caveolae; Membrane Microdomains; Cholesterol; Cell Membrane; Alzheimer Disease
PubMed: 37858892
DOI: 10.1016/j.nrleng.2023.10.003 -
International Journal of Molecular... Nov 2020The renal dopaminergic system has been identified as a modulator of sodium balance and blood pressure. According to the Centers for Disease Control and Prevention, in... (Review)
Review
The renal dopaminergic system has been identified as a modulator of sodium balance and blood pressure. According to the Centers for Disease Control and Prevention, in 2018 in the United States, almost half a million deaths included hypertension as a primary or contributing cause. Renal dopamine receptors, members of the G protein-coupled receptor family, are divided in two groups: D1-like receptors that act to keep the blood pressure in the normal range, and D2-like receptors with a variable effect on blood pressure, depending on volume status. The renal dopamine receptor function is regulated, in part, by its expression in microdomains in the plasma membrane. Lipid rafts form platforms within the plasma membrane for the organization and dynamic contact of molecules involved in numerous cellular processes such as ligand binding, membrane sorting, effector specificity, and signal transduction. Understanding all the components of lipid rafts, their interaction with renal dopamine receptors, and their signaling process offers an opportunity to unravel potential treatment targets that could halt the progression of hypertension, chronic kidney disease (CKD), and their complications.
Topics: Blood Pressure; Cell Membrane; Dopamine; Humans; Hypertension; Kidney; Membrane Microdomains; Receptors, Dopamine D1; Receptors, Dopamine D2; Signal Transduction; Sodium
PubMed: 33255376
DOI: 10.3390/ijms21238909 -
Biochimica Et Biophysica Acta.... Feb 2022Cellular membranes are fundamental building blocks regulating an extensive repertoire of biological functions. These structures contain lipids and membrane proteins that... (Review)
Review
Cellular membranes are fundamental building blocks regulating an extensive repertoire of biological functions. These structures contain lipids and membrane proteins that are known to laterally self-aggregate in the plane of the membrane, forming defined membrane nanoscale domains essential for protein activity. Membrane rafts are described as heterogeneous, dynamic, and short-lived cholesterol- and sphingolipid-enriched membrane nanodomains (10-200 nm) induced by lipid-protein and lipid-lipid interactions. Those membrane nanodomains have been extensively characterized using model membranes and in silico methods. However, despite the development of advanced fluorescence microscopy techniques, undoubted nanoscale visualization by imaging techniques of membrane rafts in the membrane of unperturbed living cells is still uncompleted, increasing the skepticism about their existence. Here, we broadly review recent biochemical and microscopy techniques used to investigate membrane rafts in living cells and we enumerate persistent open questions to answer before unlocking the mystery of membrane rafts in living cells.
Topics: Cell Membrane; Humans; Ion Transport; Membrane Microdomains; Membrane Proteins; Sphingolipids
PubMed: 34748743
DOI: 10.1016/j.bbamem.2021.183813 -
International Journal of Biological... Jan 2022High-density lipoproteins (HDLs) are heterogeneous lipoproteins that modify their composition and functionality depending on physiological or pathological conditions.... (Review)
Review
High-density lipoproteins (HDLs) are heterogeneous lipoproteins that modify their composition and functionality depending on physiological or pathological conditions. The main roles of HDL are cholesterol efflux, and anti-inflammatory and antioxidant functions. These functions can be compromised under pathological conditions. HDLs play a role in the immune system as anti-inflammatory molecules but when inflammation occurs, HDLs change their composition and carry pro-inflammatory cargo. Hence, many molecular intermediates that influence inflammatory microenvironments and cell signaling pathways can modulate HDLs structural modification and function. This review provides a comprehensive assessment of the importance of HDL composition and anti-inflammatory function in the onset and progression of atherosclerotic cardiovascular diseases. On the other hand, immune cell activation during progression of atheroma plaque formation can be influenced by HDLs through HDL-derived cholesterol depletion from lipid rafts and through HDL interaction with HDL receptors expressed on T and B lymphocytes. Cholesterol efflux is mediated by HDL receptors located in lipid rafts in peripheral cells, which undergo membrane structural modifications, and interferes with subsequent molecules interactions or intracellular signaling cascades. Regarding antigen-presentation cells such as macrophages or dendritic cells, HDL function may then modulate lymphocytes activation in immune response. Our review also contributes to the understanding of the effects exerted by HDLs in signal transduction associated to our immune cell population during chronic diseases progression.
Topics: Animals; B-Lymphocytes; Coronary Artery Disease; Disease Progression; Humans; Lipoproteins, HDL; Lymphocyte Activation; Membrane Microdomains; Receptors, Lipoprotein; Signal Transduction; T-Lymphocytes
PubMed: 34896462
DOI: 10.1016/j.ijbiomac.2021.12.009 -
The Yale Journal of Biology and Medicine Sep 2019Mycobacteria, like many other prokaryotic organisms, do not appear to have membrane-bound organelles to organize the subcellular space. Nevertheless, mycobacteria and... (Review)
Review
Mycobacteria, like many other prokaryotic organisms, do not appear to have membrane-bound organelles to organize the subcellular space. Nevertheless, mycobacteria and related bacteria grow their cell envelope in a spatially controlled manner, restricting cell elongation to the polar regions of the rod-shaped cell. This spatial organization demands that synthesized cell envelope components must be supplied to the polar ends of the cell. Because many cell envelope components are either lipids or built as lipid-anchored precursors, the plasma membrane is the major site of the biosynthesis. Thus, there are logistical questions of where in the plasma membrane these lipids and lipid precursors are made and how they are subsequently delivered to the growing poles of the cell. Our discovery of an intracellular membrane domain (IMD) fills in this gap. Currently available data suggest that the IMD is a membrane domain within the plasma membrane of mycobacteria, which mediates key biosynthetic reactions for cell envelope and other lipid biosynthetic reactions. Consistent with its role in polar growth, the IMD is enriched in the polar regions of actively growing cells and becomes less polarized when the cells experience non-growing conditions. We discuss how such membrane compartmentalization may be generated and maintained in a mycobacterial cell and why it has not evolved into a organelle. In a broader perspective, we suggest that segregation of biosynthetic pathways into different domains of a planar membrane could be more widespread than we currently think.
Topics: Membrane Lipids; Membrane Microdomains; Mycobacterium; Organelles; Stress, Physiological; Subcellular Fractions
PubMed: 31543716
DOI: No ID Found -
Biomolecules Jul 2019One of the best characterized fungal membrane microdomains is the MCC/eisosome. The MCC (membrane compartment of Can1) is an evolutionarily conserved ergosterol-rich... (Review)
Review
One of the best characterized fungal membrane microdomains is the MCC/eisosome. The MCC (membrane compartment of Can1) is an evolutionarily conserved ergosterol-rich plasma membrane domain. It is stabilized on its cytosolic face by the eisosome, a hemitubular protein complex composed of (BAR) domain-containing Pil1 and Lsp1. These two proteins bind directly to phosphatidylinositol 4,5-bisphosphate and promote the typical furrow-like shape of the microdomain, with highly curved edges and bottom. While some proteins display stable localization in the MCC/eisosome, others enter or leave it under particular conditions, such as misbalance in membrane lipid composition, changes in membrane tension, or availability of specific nutrients. These findings reveal that the MCC/eisosome, a plasma membrane microdomain with distinct morphology and lipid composition, acts as a multifaceted regulator of various cellular processes including metabolic pathways, cellular morphogenesis, signalling cascades, and mRNA decay. In this minireview, we focus on the MCC/eisosome's proposed role in the regulation of lipid metabolism. While the molecular mechanisms of the MCC/eisosome function are not completely understood, the idea of intracellular processes being regulated at the plasma membrane, the foremost barrier exposed to environmental challenges, is truly exciting.
Topics: Cell Membrane; Fungal Proteins; Fungi; Homeostasis; Lipid Metabolism; Phosphatidylinositol 4,5-Diphosphate; Protein Domains
PubMed: 31349700
DOI: 10.3390/biom9080305 -
International Journal of Molecular... Aug 2020Lipid rafts are dynamic assemblies of glycosphingolipids, sphingomyelin, cholesterol, and specific proteins which are stabilized into platforms involved in the... (Review)
Review
Lipid rafts are dynamic assemblies of glycosphingolipids, sphingomyelin, cholesterol, and specific proteins which are stabilized into platforms involved in the regulation of vital cellular processes. The rafts at the cell surface play important functions in signal transduction. Recent reports have demonstrated that lipid rafts are spatially and compositionally heterogeneous in the single-cell membrane. In this review, we summarize our recent data on living platelets using two specific probes of raft components: lysenin as a probe of sphingomyelin-rich rafts and BCθ as a probe of cholesterol-rich rafts. Sphingomyelin-rich rafts that are spatially and functionally distinct from the cholesterol-rich rafts were found at spreading platelets. Fibrin is translocated to sphingomyelin-rich rafts and platelet sphingomyelin-rich rafts act as platforms where extracellular fibrin and intracellular actomyosin join to promote clot retraction. On the other hand, the collagen receptor glycoprotein VI is known to be translocated to cholesterol-rich rafts during platelet adhesion to collagen. Furthermore, the functional roles of platelet glycosphingolipids and platelet raft-binding proteins including G protein-coupled receptors, stomatin, prohibitin, flotillin, and HflK/C-domain protein family, tetraspanin family, and calcium channels are discussed.
Topics: Animals; Blood Platelets; Cell Membrane; Cholesterol; Fibrin; Glycosphingolipids; Humans; Membrane Microdomains; Signal Transduction; Sphingomyelins
PubMed: 32748854
DOI: 10.3390/ijms21155539 -
International Journal of Molecular... Aug 2020The composition and organization of the plasma membrane play important functional and regulatory roles in integrin signaling, which direct many physiological and... (Review)
Review
The composition and organization of the plasma membrane play important functional and regulatory roles in integrin signaling, which direct many physiological and pathological processes, such as development, wound healing, immunity, thrombosis, and cancer metastasis. Membranes are comprised of regions that are thick or thin owing to spontaneous partitioning of long-chain saturated lipids from short-chain polyunsaturated lipids into domains defined as ordered and liquid-disorder domains, respectively. Liquid-ordered domains are typically 100 nm in diameter and sometimes referred to as lipid rafts. We posit that integrin β senses membrane thickness and that mechanical force on the membrane regulates integrin activation through membrane thinning. This review examines what we know about the nature and mechanism of the interaction of integrins with the plasma membrane and its effects on regulating integrins and its binding partners.
Topics: Cell Adhesion; Cell Membrane; Focal Adhesions; Humans; Integrins; Membrane Lipids; Membrane Microdomains; Membrane Proteins; Protein Binding; Signal Transduction
PubMed: 32752284
DOI: 10.3390/ijms21155531 -
Journal of the American Society of... Jan 2021In the past few decades, sphingolipids and sphingolipid metabolites have gained attention because of their essential role in the pathogenesis and progression of kidney... (Review)
Review
In the past few decades, sphingolipids and sphingolipid metabolites have gained attention because of their essential role in the pathogenesis and progression of kidney diseases. Studies in models of experimental and clinical nephropathies have described accumulation of sphingolipids and sphingolipid metabolites, and it has become clear that the intracellular sphingolipid composition of renal cells is an important determinant of renal function. Proper function of the glomerular filtration barrier depends heavily on the integrity of lipid rafts, which include sphingolipids as key components. In addition to contributing to the structural integrity of membranes, sphingolipid metabolites, such as sphingosine-1-phosphate (S1P), play important roles as second messengers regulating biologic processes, such as cell growth, differentiation, migration, and apoptosis. This review will focus on the role of S1P in renal cells and how aberrant extracellular and intracellular S1P signaling contributes to the pathogenesis and progression of kidney diseases.
Topics: Animals; Apoptosis; Cell Cycle; Cell Differentiation; Cell Movement; Gene Expression Regulation; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Kidney Transplantation; Lysophospholipids; Membrane Microdomains; Mice; Second Messenger Systems; Signal Transduction; Sphingolipids; Sphingosine
PubMed: 33376112
DOI: 10.1681/ASN.2020050697