Cholesterol regulates the cell surface expression of glycophospholipid-anchored CD14 antigen on human monocytes

Esfahani, Mohammad Reza; Bigler, Robert D.; Alfieri, John L.; Lund‐Katz, Sissel; Baum, Jonathan D.; Scerbo, L.

doi:10.1016/0005-2736(93)90204-d

Cited by 35 publications

(15 citation statements)

References 31 publications

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“…Finally, perturbation of raft domains would be expected to lead to endosomal accumulation of constructs dependent on raft domains for recycling. We interfered with raft composition by inhibiting the first committed enzyme in glycosphingolipid synthesis (glucosylceramide synthase) by N-nonyldeoxygalactonojirimycin (C9DGJ), which dramatically reduces cellular glycosphingolipid and cholesterol levels, perturbing raftdependent trafficking in cell lines (12,(45)(46)(47) and in vivo (48). Consistent with these observations and our hypothesis of raft-dependent EE-to-PM recycling, C9DGJ induced a significant and dose-dependent reduction of trLAT-WT PM localization (Fig.…”

Section: Significancesupporting

confidence: 56%

Membrane raft association is a determinant of plasma membrane localization

Diaz-Rohrer

Levental

Simons

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

193

215

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The lipid raft hypothesis proposes lateral domains driven by preferential interactions between sterols, sphingolipids, and specific proteins as a central mechanism for the regulation of membrane structure and function; however, experimental limitations in defining raft composition and properties have prevented unequivocal demonstration of their functional relevance. Here, we establish a quantitative, functional relationship between raft association and subcellular protein sorting. By systematic mutation of the transmembrane and juxtamembrane domains of a model transmembrane protein, linker for activation of T-cells (LAT), we generated a panel of variants possessing a range of raft affinities. These mutations revealed palmitoylation, transmembrane domain length, and transmembrane sequence to be critical determinants of membrane raft association. Moreover, plasma membrane (PM) localization was strictly dependent on raft partitioning across the entire panel of unrelated mutants, suggesting that raft association is necessary and sufficient for PM sorting of LAT. Abrogation of raft partitioning led to mistargeting to late endosomes/lysosomes because of a failure to recycle from early endosomes. These findings identify structural determinants of raft association and validate lipid-driven domain formation as a mechanism for endosomal protein sorting. membrane domain | endocytosis | trafficking | phase separation | microdomains R ecent advances in superresolution microscopy (1), lipid analysis (2, 3), and plasma membrane (PM) isolation (4, 5) have confirmed the coexistence of lipid-driven, fluid domains in biological membranes. The relatively ordered domains, known as "membrane rafts," have been proposed to be involved in protein sorting (6), viral/pathogen trafficking (3, 7), and PM signaling in a variety of contexts (8). However, despite the increasing evidence confirming the existence of dynamic, nanoscopic membrane rafts, the functional consequences of this phenomenon remain speculative because of the limitations of the previously used methods for defining raft association, i.e., the resistance of membrane components to solubilization by nonionic detergents (9).Lipid-mediated domains have been implicated as a mechanism for protein sorting in the latter stages of the secretory pathway (trans-Golgi network to the PM) (2, 6, 10-12), with analogous pathways mediating endosomal sorting/recycling (13,14). Raft lipids (i.e., sterols and sphingolipids) are significantly enriched at the PM (15-17), and recent observations confirm that these lipids also are enriched in sorting vesicles destined for the PM (2, 11). For proteins, several specific cytosolic signals exist for adapter/coat-mediated sorting between cellular organelles (18); in parallel, protein-lipid interactions through hydrophobic transmembrane domains (TMDs) also have been shown to regulate trafficking. For example, a strong correlation exists between the TMD length of bitopic proteins and their organelle specificity (19,20), with longer TMDs targeting proteins ...

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Section: Significancesupporting

confidence: 56%

Membrane raft association is a determinant of plasma membrane localization

Diaz-Rohrer

Levental

Simons

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

193

215

View full text Add to dashboard Cite

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“…Growth in low density lipoprotein-depleted serum lowered the expression of a hybrid GPI-anchored protein, gD1-DAF, in MDCK cells (64). Cholesterol depletion had a similar effect on the expression of the GPI-anchored protein CD14 on human monocytes (29).…”

mentioning

confidence: 79%

Sorting and Intracellular Trafficking of a Glycosylphosphatidylinositol-anchored Protein and Two Hybrid Transmembrane Proteins with the Same Ectodomain in Madin-Darby Canine Kidney Epithelial Cells

Arreaza

Brown

1995

Journal of Biological Chemistry

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We compared the trafficking of the glycosylphosphatidylinositol (GPI)-anchored placental alkaline phosphatase (PLAP) and two chimeric transmembrane proteins containing the PLAP ectodomain in stably transfected Madin-Darby canine kidney epithelial cells to determine whether different mechanisms might be used in apical sorting of GPI-anchored and transmembrane proteins. PLAP-G, which contained the transmembrane and cytoplasmic domains of the vesicular stomatitis virus glycoprotein, was delivered directly to the basolateral surface. PLAP-HA contained the transmembrane and cytoplasmic domains of influenza hemagglutinin. Both PLAP and PLAP-HA were delivered directly to the apical membrane. PLAP becomes insoluble in Triton X-100 during biosynthetic transport, as it associates with detergent-resistant membranes. Neither hybrid protein was detergent insoluble, though the small amount of PLAP that was missorted to the basolateral surface was insoluble. We examined the effects of three drugs known to interfere with membrane trafficking on sorting and delivery of PLAP and the hybrid proteins. Monensin had no effect on sorting or surface expression of any of the proteins. Nocodazole affected the sorting of both PLAP and PLAP-HA but not of PLAP-G. Brefeldin A appeared to disrupt the sorting of PLAP and PLAP-HA but not of PLAP-G. This conclusion was tempered by the observation that this drug affected the distribution of proteins at the cell surface. Thus, sorting and transport of GPIanchored and apical transmembrane proteins are similar in a number of respects.

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“…LDL-C, indeed, has been reported to affect host immune functions. LDL is required for the optimal expression of the Fc receptor or CD14, which mediates phagocytosis of human monocytes, and a high-fat diet has been shown to decrease the antitumor activity of macrophages in mice [19,20,21]. Moreover, high LDL levels have been reported to inhibit T-cell proliferation [22].…”

Section: Discussionmentioning

confidence: 99%

Serum Lipid Profile in Colorectal Cancer Patients with and without Synchronous Distant Metastases

et al. 2005

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Objective: In this study, the serum lipid profile, including total cholesterol (TC), triglycerides (TG), high-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C), has been investigated in colorectal cancer patients (CRC) with and without synchronous distant metastases. The aim of this study was to verify whether the presence of metastases was associated to serum lipid abnormalities, and whether lipoprotein abnormalities were linked to the nutritional status. Methods: The fasting serum lipid profile was examined in 84 CRC patients using colorimetric methods. To determine the nutritional status, the body mass index (BMI) was calculated and serum albumin was measured. Results: Patients with distant metastases showed significantly higher levels of TC, LDL-C and the LDL-C/HDL-C ratio than patients without metastases (p< 0.05). The presence of metastases was positively associated with TC, LDL-C and the LDL-C/HDL-C ratio, being independent of sex, age and BMI. Conclusions: Elevated serum lipid levels may facilitate the development of distant metastasis in CRC patients.

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Cholesterol regulates the cell surface expression of glycophospholipid-anchored CD14 antigen on human monocytes

Cited by 35 publications

References 31 publications

Membrane raft association is a determinant of plasma membrane localization

Membrane raft association is a determinant of plasma membrane localization

Sorting and Intracellular Trafficking of a Glycosylphosphatidylinositol-anchored Protein and Two Hybrid Transmembrane Proteins with the Same Ectodomain in Madin-Darby Canine Kidney Epithelial Cells

Serum Lipid Profile in Colorectal Cancer Patients with and without Synchronous Distant Metastases

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