Disease relevance of Membrane Microdomains

• CD4 receptor localized to non-raft membrane microdomains supports HIV-1 entry. Identification of a novel raft localization marker in CD4 [1].
• We have previously shown that fibroblast growth factor-2 (FGF2) induced a specific signaling response within a lipid raft membrane microdomain in human neuroblastoma cells characterized by the tyrosine phosphorylation of a p80 phosphoprotein [2].
• Organization of the vesicular stomatitis virus glycoprotein into membrane microdomains occurs independently of intracellular viral components [3].
• Cholesterol-rich membrane microdomains mediate cell cycle arrest induced by Actinobacillus actinomycetemcomitans cytolethal-distending toxin [4].
• Influenza virus hemagglutinin (HA) and neuraminidase (NA) are known to associate with lipid rafts, membrane microdomains comprised of densely packed cholesterol and sphingolipids [5].

Psychiatry related information on Membrane Microdomains

• Thus, altering cholesterol levels may influence the development of Alzheimer's disease (AD) by influencing production and deposition of Abeta within cholesterol rich membrane microdomains [6].

High impact information on Membrane Microdomains

• Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain [7].
• Other lines of research, addressing the structure of planar biological membranes, have revealed the existence of cholesterol-based membrane microdomains [8].
• Here we show that ephrin-A5, which is attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidylinositol-anchor, induces compartmentalized signaling within a caveolae-like membrane microdomain when bound to the extracellular domain of its cognate Eph receptor [9].
• Here we show that upon TNFalpha binding, TNFR1 translocates to cholesterol- and sphingolipid-enriched membrane microdomains, termed lipid rafts, where it associates with the Ser/Thr kinase RIP and the adaptor proteins TRADD and TRAF2, forming a signaling complex [10].
• Distinct patterns of membrane microdomain partitioning in Th1 and th2 cells [11].

Biological context of Membrane Microdomains

• Cholesterol-based membrane microdomains, or lipid rafts, are believed to play important, yet poorly defined, roles in protein trafficking and signal transduction [12].
• Disruption of cholesterol-containing membrane microdomains with filipin prevented the degradation of FcgammaRIIA but did not inhibit the stimulation of the pattern of tyrosine phosphorylation or the mobilization of calcium that followed FcgammaRIIA cross-linking [13].
• Our findings suggest that binding of Ezetimibe to APN from the lumen of the small intestine blocks endocytosis of cholesterol-rich membrane microdomains, thereby limiting intestinal cholesterol absorption [14].
• We also show that the juxtamembrane cysteine repeats in the LMP2A C terminus are the major targets for palmitoylation but that this acylation is not required for targeting of LMP2A to detergent-insoluble glycolipid-enriched membrane microdomains [15].
• Role of membrane microdomains in PTH-mediated down-regulation of NaPi-IIa in opossum kidney cells [16].

Anatomical context of Membrane Microdomains

• LAT is central to T cell activation and is a novel linker molecule shown to require targeting to membrane microdomains for signaling [17].
• The role of MAL in the formation, stabilisation and maintenance of glycosphingolipid-enriched membrane microdomains and its contribution to specific membrane properties in myelin and epithelial cells are discussed [18].
• Immunofluorescence staining on hepatocyte couplets for both caveolin-1 and cholera toxin B showed a punctate distribution on both the apical and basolateral plasma membranes, consistent with localized membrane microdomains [19].
• Caveolae are cholesterol-rich membrane microdomains that, along with their marker protein caveolin-1 (Cav-1), have been implicated in the compartmentalization and regulation of certain signaling events [20].
• Recently, we demonstrated that binding of CD20 Abs to B cells induces the rapid redistribution of up to 95% of CD20 molecules to low density, detergent-insoluble membrane microdomains and induces the appearance of an approximately 50-kDa tyrosine-phosphorylated protein in the same compartment [21].

Associations of Membrane Microdomains with chemical compounds

• We here show that insolubility of NADPH oxidase subunits in nonionic detergents TX-100, Brij-58, and Brij-98 is a consequence of inclusion into cholesterol-enriched membrane microdomains (lipid rafts) [22].
• Thus, stimulation of a mitogenic pathway by gp120 appears to require receptor binding in the context of membrane microdomains [23].
• The finding that GPI-anchored proteins are present in detergent-insoluble complexes with several tyrosine kinases of the Src family suggested that these complexes may represent membrane microdomains involved in the transduction of signals to the cell interior [24].
• Ceramide appears to modify preexisting sphingolipid-rich membrane microdomains to fuse and form ceramide-enriched signaling platforms that serve to cluster CD40 ligand [25].
• It has been reported that annexin A2 is involved in binding to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and in inducing membrane microdomain formation [26].

Gene context of Membrane Microdomains

• There is growing evidence that cholesterol- and sphingolipid-rich membrane microdomains are involved in regulating trafficking and processing of APP [27].
• Relationships between EGFR signaling-competent and endocytosis-competent membrane microdomains [28].
• Enhanced signaling is due in part to the ability of the CD19/CD21/CD81 complex to stabilize the BCR in sphingolipid- and cholesterol-rich membrane microdomains termed lipid rafts [29].
• PS1 and BACE are located in detergent-resistant membranes (DRMs), well structured membrane microdomains exhibiting high levels of cholesterol, and caveolin-1 [30].
• We conclude that in human proximal tubule cells, CD40 and TRAF6 reside in separate low-density, detergent-insoluble membrane microdomains, or rafts, and on activation translocate and associate with one another probably via zinc-finger domains in the soluble or cytoplasmic compartment [31].

Analytical, diagnostic and therapeutic context of Membrane Microdomains

• The association of the presenilins with detergent-insoluble, low-density membrane microdomains, following the isolation of these structures from cerebral cortex by solubilization in Triton X-100 and subsequent sucrose density gradient centrifugation, was also examined [32].
• In addition, we present data demonstrating that these molecules associate with TLR4 and accumulate in membrane microdomains following LPS ligation [33].

References