scholarly journals Sphingolipids: membrane microdomains in brain development, function and neurological diseases

Open Biology ◽  
2017 ◽  
Vol 7 (5) ◽  
pp. 170069 ◽  
Author(s):  
Anne S. B. Olsen ◽  
Nils J. Færgeman
Keyword(s):  
Plasma Membrane ◽  
Brain Development ◽  
Plasma Membranes ◽  
Neurological Diseases ◽  
Sphingolipid Metabolism ◽  
Membrane Microdomains ◽  
Vast Number ◽  
Cellular Events ◽  
Long Time ◽  
And Function

Sphingolipids are highly enriched in the nervous system where they are pivotal constituents of the plasma membranes and are important for proper brain development and functions. Sphingolipids are not merely structural elements, but are also recognized as regulators of cellular events by their ability to form microdomains in the plasma membrane. The significance of such compartmentalization spans broadly from being involved in differentiation of neurons and synaptic transmission to neuronal–glial interactions and myelin stability. Thus, perturbations of the sphingolipid metabolism can lead to rearrangements in the plasma membrane, which has been linked to the development of various neurological diseases. Studying microdomains and their functions has for a long time been synonymous with studying the role of cholesterol. However, it is becoming increasingly clear that microdomains are very heterogeneous, which among others can be ascribed to the vast number of sphingolipids. In this review, we discuss the importance of microdomains with emphasis on sphingolipids in brain development and function as well as how disruption of the sphingolipid metabolism (and hence microdomains) contributes to the pathogenesis of several neurological diseases.

Membrane microdomains: lessons from microscopy

1995 ◽  
Vol 53 ◽  
pp. 776-777
Author(s):  
J.M. Robinson ◽  
J.M Oliver
Keyword(s):  
Spatial Distribution ◽  
Plasma Membrane ◽  
Epithelial Cells ◽  
Plasma Membranes ◽  
Cell Types ◽  
Imaging Modalities ◽  
Membrane Microdomains ◽  
Membrane Domains ◽  
Lateral Heterogeneity ◽  
Functional Importance

Specialized regions of plasma membranes displaying lateral heterogeneity are the focus of this Symposium. Specialized membrane domains are known for certain cell types such as differentiated epithelial cells where lateral heterogeneity in lipids and proteins exists between the apical and basolateral portions of the plasma membrane. Lateral heterogeneity and the presence of microdomains in membranes that are uniform in appearance have been more difficult to establish. Nonetheless a number of studies have provided evidence for membrane microdomains and indicated a functional importance for these structures.This symposium will focus on the use of various imaging modalities and related approaches to define membrane microdomains in a number of cell types. The importance of existing as well as emerging imaging technologies for use in the elucidation of membrane microdomains will be highlighted. The organization of membrane microdomains in terms of dimensions and spatial distribution is of considerable interest and will be addressed in this Symposium.

scholarly journals Pseudotypes of Vesicular Stomatitis Virus with CD4 Formed by Clustering of Membrane Microdomains during Budding

2005 ◽  
Vol 79 (11) ◽  
pp. 7077-7086 ◽  
Author(s):  
Erica L. Brown ◽  
Douglas S. Lyles
Keyword(s):  
Plasma Membrane ◽  
G Protein ◽  
Lipid Rafts ◽  
Immunoelectron Microscopy ◽  
Vesicular Stomatitis Virus ◽  
Plasma Membranes ◽  
Membrane Microdomains ◽  
Virus Budding ◽  
Vesicular Stomatitis ◽  
Membrane Components

ABSTRACT Many plasma membrane components are organized into detergent-resistant membrane microdomains referred to as lipid rafts. However, there is much less information about the organization of membrane components into microdomains outside of lipid rafts. Furthermore, there are few approaches to determine whether different membrane components are colocalized in microdomains as small as lipid rafts. We have previously described a new method of determining the extent of organization of proteins into membrane microdomains by analyzing the distribution of pairwise distances between immunogold particles in immunoelectron micrographs. We used this method to analyze the microdomains involved in the incorporation of the T-cell antigen CD4 into the envelope of vesicular stomatitis virus (VSV). In cells infected with a recombinant virus that expresses CD4 from the viral genome, both CD4 and the VSV envelope glycoprotein (G protein) were found in detergent-soluble (nonraft) membrane fractions. However, analysis of the distribution of CD4 and G protein in plasma membranes by immunoelectron microscopy showed that both were organized into membrane microdomains of similar sizes, approximately 100 to 150 nm. In regions of plasma membrane outside of virus budding sites, CD4 and G protein were present in separate membrane microdomains, as shown by double-label immunoelectron microscopy data. However, virus budding occurred from membrane microdomains that contained both G protein and CD4, and extended to approximately 300 nm, indicating that VSV pseudotype formation with CD4 occurs by clustering of G protein- and CD4-containing microdomains.

Structural diversity of band 4.1 superfamily members

1994 ◽  
Vol 107 (7) ◽  
pp. 1921-1928 ◽  
Author(s):  
K. Takeuchi ◽  
A. Kawashima ◽  
A. Nagafuchi ◽  
S. Tsukita
Keyword(s):  
Plasma Membrane ◽  
Tyrosine Kinases ◽  
Plasma Membranes ◽  
Structural Diversity ◽  
Gene Families ◽  
Cdna Clones ◽  
New Members ◽  
F9 Cells ◽  
Novel Proteins ◽  
Cellular Events

Several proteins contain the domain homologous to the N-terminal half of band 4.1 protein, indicating the existence of a superfamily. The members of this ‘band 4.1’ superfamily are thought to play crucial roles in the regulation of cytoskeleton-plasma membrane interaction just beneath plasma membranes. We examined the structural diversity of this superfamily by means of the polymerase chain reaction using synthesized mixed primers. We thus identified many members of the band 4.1 superfamily that were expressed in mouse teratocarcinoma F9 cells and mouse brain tissue. In total, 15 cDNA clones were obtained; 8 were identical to the corresponding parts of cDNAs for the known members, while 7 appeared to encode novel proteins (NBL1-7: novel band 4.1-like proteins). Sequence analyses of these clones revealed that the band 4.1 superfamily can be subdivided into 5 gene families; band 4.1 protein, ERM (ezrin/radixin/moesin/merlin/NBL6/NBL7+ ++), talin, PTPH1 (PTPH1/PTPMEG/NBL1-3), and NBL4 (NBL4/NBL5) families. The NBL4 family was first identified here, and the full-length cDNA encoding NBL4 was cloned. The deduced amino acid sequence revealed a myristoylation site, as well as phosphorylation sites for A-kinase and tyrosine kinases in its N-terminal half, suggesting its involvement in the phosphorylation-dependent regulation of cellular events just beneath the plasma membrane. In this study, we describe the initial characterization of these new members and discuss the evolution of the band 4.1 superfamily.

scholarly journals Structure and Function of the Plasma Membrane

1968 ◽  
Vol 52 (1) ◽  
pp. 257-278 ◽  
Author(s):  
Edward D. Korn
Keyword(s):  
Plasma Membrane ◽  
Plasma Membranes ◽  
Current Knowledge ◽  
Structure And Function ◽  
Attractive Alternative ◽  
Membrane Function ◽  
Classical Models ◽  
And Function ◽  
Direct Attack ◽  
Membrane Biosynthesis

The paucimolecular unit membrane model of the structure of the plasma membrane is critically reviewed in relation to current knowledge of the chemical and enzymatic composition of isolated plasma membranes, the properties of phospholipids, the chemistry of fixation for electron microscopy, the conformation of membrane proteins, the nature of the lipid-protein bonds in membranes, and possible mechanisms of transmembrane transport and membrane biosynthesis. It is concluded that the classical models, although not disproven, are not well supported by, and are difficult to reconcile with, the data now available. On the other hand, although a model based on lipoprotein subunits is, from a biochemical perspective, an attractive alternative, it too is far from proven. Many of the questions may be resolved by studies of membrane function and membrane biosynthesis rather than by a direct attack on membrane structure.

scholarly journals Quantification of phosphoinositides reveals strong enrichment of PIP2 in HIV-1 compared to producer cell membranes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Frauke Mücksch ◽  
Mevlut Citir ◽  
Christian Lüchtenborg ◽  
Bärbel Glass ◽  
Alexis Traynor-Kaplan ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Quantitative Analysis ◽  
Plasma Membranes ◽  
Membrane Microdomains ◽  
Cell Plasma ◽  
Producer Cell ◽  
Transient Interactions ◽  
Molecular Anatomy ◽  
Lipid Compounds ◽  
Hiv 1

AbstractHuman immunodeficiency virus type 1 (HIV-1) acquires its lipid envelope during budding from the plasma membrane of the host cell. Various studies indicated that HIV-1 membranes differ from producer cell plasma membranes, suggesting budding from specialized membrane microdomains. The phosphoinositide PI(4,5)P2 has been of particular interest since PI(4,5)P2 is needed to recruit the viral structural polyprotein Gag to the plasma membrane and thus facilitates viral morphogenesis. While there is evidence for an enrichment of PIP2 in HIV-1, fully quantitative analysis of all phosphoinositides remains technically challenging and therefore has not been reported, yet. Here, we present a comprehensive analysis of the lipid content of HIV-1 and of plasma membranes from infected and non-infected producer cells, resulting in a total of 478 quantified lipid compounds, including molecular species distribution of 25 different lipid classes. Quantitative analyses of phosphoinositides revealed strong enrichment of PIP2, but also of PIP3, in the viral compared to the producer cell plasma membrane. We calculated an average of ca. 8,000 PIP2 molecules per HIV-1 particle, three times more than Gag. We speculate that the high density of PIP2 at the HIV-1 assembly site is mediated by transient interactions with viral Gag polyproteins, facilitating PIP2 concentration in this microdomain. These results are consistent with our previous observation that PIP2 is not only required for recruiting, but also for stably maintaining Gag at the plasma membrane. We believe that this quantitative analysis of the molecular anatomy of the HIV-1 lipid envelope may serve as standard reference for future investigations.

scholarly journals Structure and cholesterol domain dynamics of an enriched caveolae/raft isolate

2004 ◽  
Vol 382 (2) ◽  
pp. 451-461 ◽  
Author(s):  
Adalberto M. GALLEGOS ◽  
Avery L. McINTOSH ◽  
Barbara P. ATSHAVES ◽  
Friedhelm SCHROEDER
Keyword(s):  
Plasma Membrane ◽  
Plasma Membranes ◽  
Initial Rate ◽  
Probe Molecules ◽  
Factors Affecting ◽  
Raft Domains ◽  
And Function ◽  
Sterol Carrier Protein 2 ◽  
Multiple Probe ◽  
Domain Dynamics

Despite the importance of cholesterol in the formation and function of caveolar microdomains in plasma membranes, almost nothing is known regarding the structural properties, cholesterol dynamics or intracellular factors affecting caveolar cholesterol dynamics. A non-detergent method was employed to isolate caveolae/raft domains from purified plasma membranes of murine fibroblasts. A series of fluorescent lipid probe molecules or a fluorescent cholesterol analogue, dehydroergosterol, were then incorporated into the caveolae/raft domains to show that: (i) fluorescence polarization of the multiple probe molecules {diphenylhexatriene analogues, DiI18 (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate), parinaric acids and NBD-stearic acid {12-(N-methyl)-N-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-octadecanoic acid} indicated that acyl chains in caveolae/raft domains were significantly less ‘fluid’ (i.e. more rigid) and the transbilayer ‘fluidity gradient’ was 4.4-fold greater than in plasma membranes; (ii) although sterol was more ordered in caveolae/raft domains than plasma membranes, spontaneous sterol transfer from caveolae/raft domains was faster (initial rate, 32%; half-time, t1/2, 57%) than from the plasma membrane; (iii) although kinetic analysis showed similar proportions of exchangeable and non-exchangeable sterol pools in caveolae/raft domains and plasma membranes, addition of SCP-2 (sterol carrier protein-2) 1.3-fold more selectively increased sterol transfer from caveolae/raft domains by decreasing the t1/2 (50%) and increasing the initial rate (5-fold); (iv) SCP-2 was also 2-fold more selective in decreasing the amount of non-exchangeable sterol in caveolae/raft domains compared with plasma membranes, such that nearly 80% of caveolar/raft sterol became exchangeable. In summary, although caveolae/raft lipids were less fluid than those of plasma membranes, sterol domains in caveolae/rafts were more spontaneously exchangeable and more affected by SCP-2 than those of the bulk plasma membranes. Thus caveolae/raft domains isolated without the use of detergents display unique structure, cholesterol domain kinetics and responsiveness to SCP-2 as compared with the parent plasma membrane.

Nicotinic acetylcholine receptor α7 regulates cAMP signal within lipid rafts

2003 ◽  
Vol 285 (3) ◽  
pp. C567-C574 ◽  
Author(s):  
Jin Oshikawa ◽  
Yoshiyuki Toya ◽  
Takayuki Fujita ◽  
Masato Egawa ◽  
Junichi Kawabe ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Plasma Membranes ◽  
Gradient Centrifugation ◽  
Membrane Microdomains ◽  
Cholesterol Depletion ◽  
Nicotinic Acetylcholine ◽  
Density Fractions

Neuronal nicotinic acetylcholine receptors (nAChRs) are made of multiple subunits with diversified functions. The nAChR α7-subunit has a property of high Ca2+ permeability and may have specific functions and localization within the plasma membrane as a signal transduction molecule. In PC-12 cells, fractionation by sucrose gradient centrifugation revealed that nAChRα7 existed in low-density, cholesterol-enriched plasma membrane microdomains known as lipid rafts where flotillin also exists. In contrast, nAChR α5- and β2-subunits were located in high-density fractions, out of the lipid rafts. Type 6 adenylyl cyclase (AC6), a calcium-inhibitable isoform, was also found in lipid rafts and was coimmunoprecipitated with nAChRα7. Cholesterol depletion from plasma membranes with methyl-β-cyclodextrin redistributed nAChRα7 and AC6 diffusely within plasma membranes. Nicotine stimulation reduced forskolin-stimulated AC activity by 35%, and this inhibition was negated by either treatment with α-bungarotoxin, a specific antagonist of nAChRα7, or cholesterol depletion from plasma membranes. The effect of cholesterol depletion was negated by the addition of cholesterol. These data suggest that nAChRα7 has a specific membrane localization relative to other nAChR subunits and that lipid rafts are necessary to localize nAChRα7 with AC within plasma membranes. In addition, nAChRα7 may regulate the AC activity via Ca2+ within lipid rafts.

Chronic alcohol feeding and its withdrawal on the structure and function of the rat liver plasma membrane: a study with 125I-labelled glucagon binding as a metabolic probe

1982 ◽  
Vol 60 (9) ◽  
pp. 1171-1176 ◽  
Author(s):  
Hung Lee ◽  
E. A. Hosein
Keyword(s):  
Plasma Membrane ◽  
Rat Liver ◽  
Plasma Membranes ◽  
Structure And Function ◽  
Scatchard Analysis ◽  
Chronic Alcohol ◽  
Alcohol Administration ◽  
Liver Plasma Membranes ◽  
And Function ◽  
Chronic Alcohol Administration

The effect of chronic alcohol administration on the structure and function of the rat liver plasma membranes has been investigated. Chronic alcohol administration did not affect the yield of these membranes using conventional isolation procedures. The extent of plasma membrane enrichment or contamination with other interior membranes was identical in the control and alcoholic preparations. The binding of 125I-labelled glucagon to these experimental liver plasma membranes was significantly decreased. Scatchard analysis of the high affinity sites showed a significant reduction [Formula: see text] in receptor number rather than binding affinity, which was not altered. This anomaly persisted through 72-h withdrawal of alcohol. These data suggest that very stable changes were induced in these liver plasma membranes after prolonged alcohol ingestion.

scholarly journals Disruption of ankyrin B and caveolin-1 interaction sites alters Na+,K+-ATPase lateral diffusion in HEK293 cell plasma membranes

2017 ◽  
Author(s):  
Cornelia Junghans ◽  
Vladana Vukojević ◽  
Neslihan N. Tavraz ◽  
Eugene G. Maksimov ◽  
Werner Zuschratter ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Plasma Membranes ◽  
Matrix Proteins ◽  
Membrane Microdomains ◽  
Membrane Targeting ◽  
Α Subunit ◽  
Caveolin 1 ◽  
Interaction Sites ◽  
Ankyrin B ◽  
Cellular Matrix

AbstractThe Na+,K+-ATPase is a plasma membrane ion transporter of high physiological importance for ion homeostasis and cellular excitability in electrically active tissues. Mutations in the genes coding for Na+,K+-ATPase α-subunit isoforms lead to severe human pathologies including Familial Hemiplegic Migraine type 2 (FHM2), Alternating Hemiplegia of Childhood (AHC), Rapid Dystonia Parkinsonism (RDP) or epilepsy. Many of the reported mutations lead to change- or loss-of-function effects, whereas others do not alter the functional properties, but lead to e.g. reduced protein stability, reduced protein expression or defective plasma membrane targeting. Na+,K+-ATPase frequently assembles with other membrane transporters or cellular matrix proteins in specialized plasma membrane microdomains, but the effects of these interactions on targeting or protein mobility are elusive so far. Mutational disruption of established interaction motifs of the Na+,K+-ATPase with ankyrin B and caveolin-1 are expected to result in changes in plasma membrane targeting, changes of the localization pattern, and of the diffusion behavior of the enzyme. We studied the consequences of mutations in these binding sites by monitoring diffusion of eGFP-labeled Na+,K+-ATPase constructs in the plasma membrane of living HEK293T cells by fluorescence correlation spectroscopy (FCS) as well as fluorescence recovery after photobleaching (FRAP) or photoswitching (FRAS) and observed significant differences compared to the wild-type enzyme, with synergistic effects for combinations of interaction site mutations. These measurements expand the possibilities to study the consequences of Na+,K+-ATPase mutations and provide information about the interaction of Na+,K+-ATPase α2-isoform with cellular matrix proteins, the cytoskeleton or other membrane protein complexes.

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