scholarly journals Bioactive Ether Lipids: Primordial Modulators of Cellular Signaling

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 41
Author(s):  
Nikhil Rangholia ◽  
Tina M. Leisner ◽  
Stephen P. Holly
Keyword(s):  
Mammalian Cells ◽  
Ether Lipid ◽  
Cell Surface Receptor ◽  
Ether Lipids ◽  
Permeable Barrier ◽  
Essential Components ◽  
Intracellular Regulation ◽  
Enzymatic Cascades ◽  
Surface Receptor ◽  
Functional Mechanisms

The primacy of lipids as essential components of cellular membranes is conserved across taxonomic domains. In addition to this crucial role as a semi-permeable barrier, lipids are also increasingly recognized as important signaling molecules with diverse functional mechanisms ranging from cell surface receptor binding to the intracellular regulation of enzymatic cascades. In this review, we focus on ether lipids, an ancient family of lipids having ether-linked structures that chemically differ from their more prevalent acyl relatives. In particular, we examine ether lipid biosynthesis in the peroxisome of mammalian cells, the roles of selected glycerolipids and glycerophospholipids in signal transduction in both prokaryotes and eukaryotes, and finally, the potential therapeutic contributions of synthetic ether lipids to the treatment of cancer.

scholarly journals Endocytic Delivery of Vancomycin Mediated by a Synthetic Cell Surface Receptor:  Rescue of Bacterially Infected Mammalian Cells and Tissue Targeting In Vivo

2007 ◽  
Vol 129 (2) ◽  
pp. 268-269 ◽  
Author(s):  
Siwarutt Boonyarattanakalin ◽  
Jianfang Hu ◽  
Sheryl A. Dykstra-Rummel ◽  
Avery August ◽  
Blake R. Peterson
Keyword(s):  
Cell Surface ◽  
Mammalian Cells ◽  
Cell Surface Receptor ◽  
Synthetic Cell ◽  
Tissue Targeting ◽  
Surface Receptor

scholarly journals Neuropilin-1 and heparan sulfate proteoglycans cooperate in cellular uptake of nanoparticles functionalized by cationic cell-penetrating peptides

2015 ◽  
Vol 1 (10) ◽  
pp. e1500821 ◽  
Author(s):  
Hong-Bo Pang ◽  
Gary B. Braun ◽  
Erkki Ruoslahti
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Vascular Permeability ◽  
Mammalian Cells ◽  
Cell Penetrating Peptides ◽  
Proteolytic Processing ◽  
Cell Surface Receptor ◽  
Neuropilin 1 ◽  
Cell Penetrating ◽  
Surface Receptor

Cell-penetrating peptides (CPPs) have been widely used to deliver nanomaterials and other types of macromolecules into mammalian cells for therapeutic and diagnostic use. Cationic CPPs that bind to heparan sulfate (HS) proteoglycans on the cell surface induce potent endocytosis; however, the role of other surface receptors in this process is unclear. We describe the convergence of an HS-dependent pathway with the C-end rule (CendR) mechanism that enables peptide ligation with neuropilin-1 (NRP1), a cell surface receptor known to be involved in angiogenesis and vascular permeability. NRP1 binds peptides carrying a positive residue at the carboxyl terminus, a feature that is compatible with cationic CPPs, either intact or after proteolytic processing. We used CPP and CendR peptides, as well as HS- and NRP1-binding motifs from semaphorins, to explore the commonalities and differences of the HS and NRP1 pathways. We show that the CendR-NRP1 interaction determines the ability of CPPs to induce vascular permeability. We also show at the ultrastructural level, using a novel cell entry synchronization method, that both the HS and NRP1 pathways can initiate a macropinocytosis-like process and visualize these CPP-cargo complexes going through various endosomal compartments. Our results provide new insights into how CPPs exploit multiple surface receptor pathways for intracellular delivery.

scholarly journals Specific Capture of Mammalian Cells by Cell Surface Receptor Binding to Ligand Immobilized on Gold Thin Films

2006 ◽  
Vol 5 (7) ◽  
pp. 1580-1585 ◽  
Author(s):  
Dora Peelen ◽  
Voula Kodoyianni ◽  
Jieun Lee ◽  
Ting Zheng ◽  
Michael R. Shortreed ◽  
...  
Keyword(s):  
Thin Films ◽  
Cell Surface ◽  
Receptor Binding ◽  
Mammalian Cells ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
Gold Thin Films

scholarly journals Subcellular Redistribution of Pit-2 PiTransporter/Amphotropic Leukemia Virus (A-MuLV) Receptor in A-MuLV-Infected NIH 3T3 Fibroblasts: Involvement in Superinfection Interference

2000 ◽  
Vol 74 (6) ◽  
pp. 2847-2854 ◽  
Author(s):  
Zsolt Jobbagy ◽  
Susan Garfield ◽  
Lisa Baptiste ◽  
Maribeth V. Eiden ◽  
Wayne B. Anderson
Keyword(s):  
Plasma Membrane ◽  
Mammalian Cells ◽  
Leukemia Virus ◽  
Cell Surface Receptor ◽  
3T3 Cells ◽  
Sodium Dependent ◽  
Surface Receptor ◽  
A Cell ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT Amphotropic murine leukemia virus (A-MuLV) utilizes the Pit-2 sodium-dependent phosphate transporter as a cell surface receptor to infect mammalian cells. Previous studies established that infection of cells with A-MuLV resulted in the specific down-modulation of phosphate uptake mediated by Pit-2 and in resistance to superinfection with A-MuLV. To study the mechanisms underlying these phenomena, we constructed plasmids capable of efficiently expressing ɛ epitope- and green fluorescent protein (GFP)-tagged human Pit-2 proteins in mammalian cells. Overexpression of ɛ-epitope-tagged Pit-2 transporters in NIH 3T3 cells resulted in a marked increase in sodium-dependent Pi uptake. This increase in Piuptake was specifically blocked by A-MuLV infection but not by infection with ecotropic MuLV (E-MuLV) (which utilizes a cationic amino acid transporter, not Pit-2, as a cell surface receptor). These data, together with the finding that the tagged Pit-2 transporters retained their A-MuLV receptor function, indicate that the insertion of epitope tags does not affect either retrovirus receptor or Pitransporter function. The overexpressed epitope-tagged transporters were detected in cell lysates, by Western blot analysis using both ɛ-epitope- and GFP-specific antibodies as well as with Pit-2 antiserum. Both the epitope- and GFP-tagged transporters showed almost exclusive plasma membrane localization when expressed in NIH 3T3 cells, as determined by laser scanning confocal microscopy. Importantly, when NIH 3T3 cells expressing these proteins were productively infected with A-MuLV, the tagged transporters and receptors were no longer detected in the plasma membrane but rather were localized to a punctate structure within the cytosolic compartment distinct from Golgi, endoplasmic reticulum, endosomes, lysosomes, and mitochondria. The intracellular Pit-2 pool colocalized with the virus in A-MuLV-infected cells. A similar redistribution of the tagged Pit-2 proteins was not observed following infection with E-MuLV, indicating that the redistribution of Pit-2 is not directly attributable to general effects associated with retroviral infection but rather is a specific consequence of A-MuLV–Pit-2 interactions.

Endocytosis

1997 ◽  
Vol 77 (3) ◽  
pp. 759-803 ◽  
Author(s):  
S. Mukherjee ◽  
R. N. Ghosh ◽  
F. R. Maxfield
Keyword(s):  
Antigen Presentation ◽  
Mammalian Cells ◽  
Membrane Lipids ◽  
Extracellular Fluid ◽  
Cell Polarization ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Coated Pits ◽  
Surface Receptor ◽  
Membrane Components

Mammalian cells take up extracellular material by a variety of different mechanisms that are collectively termed endocytosis. Endocytic mechanisms serve many important cellular functions including the uptake of extracellular nutrients, regulation of cell-surface receptor expression, maintenance of cell polarity, and antigen presentation. Endocytic pathways are also utilized by viruses, toxins, and symbiotic microorganisms to gain entry into cells. One of the best-characterized endocytic mechanisms is receptor-mediated endocytosis via clathrin-coated pits. This type of endocytosis constitutes the major emphasis of this review, with a brief discussion of other endocytic mechanisms and their comparison with the receptor-mediated pathway. This review describes and evaluates critically current understanding of the mechanisms of entry of plasma membrane components such as the receptor-ligand complexes and membrane lipids as well as the extracellular fluid into cells. The intracellular sorting and trafficking of these molecules upon internalization are also described. The roles of endocytosis in physiological and pathological processes are discussed. These include maintenance of cell polarization, antigen presentation, glucose transport, atherosclerosis, Alzheimer's disease, and the endocytosis of toxins and viruses.

scholarly journals Dictyostelium discoideum Dgat2 Can Substitute for the Essential Function of Dgat1 in Triglyceride Production but Not in Ether Lipid Synthesis

2014 ◽  
Vol 13 (4) ◽  
pp. 517-526 ◽  
Author(s):  
Xiaoli Du ◽  
Cornelia Herrfurth ◽  
Thomas Gottlieb ◽  
Steffen Kawelke ◽  
Kristin Feussner ◽  
...  
Keyword(s):  
Dictyostelium Discoideum ◽  
Mammalian Cells ◽  
Lipid Droplets ◽  
Lipid Synthesis ◽  
Ether Lipid ◽  
Natural Food ◽  
Ether Lipids ◽  
Double Knockout ◽  
Content Type ◽  
Knockout Mutants

ABSTRACT Triacylglycerol (TAG), the common energy storage molecule, is formed from diacylglycerol and a coenzyme A-activated fatty acid by the action of an acyl coenzyme A:diacylglycerol acyltransferase (DGAT). In order to conduct this step, most organisms rely on more than one enzyme. The two main candidates in Dictyostelium discoideum are Dgat1 and Dgat2. We show, by creating single and double knockout mutants, that the endoplasmic reticulum (ER)-localized Dgat1 enzyme provides the predominant activity, whereas the lipid droplet constituent Dgat2 contributes less activity. This situation may be opposite from what is seen in mammalian cells. Dictyostelium Dgat2 is specialized for the synthesis of TAG, as is the mammalian enzyme. In contrast, mammalian DGAT1 is more promiscuous regarding its substrates, producing diacylglycerol, retinyl esters, and waxes in addition to TAG. The Dictyostelium Dgat1, however, produces TAG, wax esters, and, most interestingly, also neutral ether lipids, which represent a significant constituent of lipid droplets. Ether lipids had also been found in mammalian lipid droplets, but the role of DGAT1 in their synthesis was unknown. The ability to form TAG through either Dgat1 or Dgat2 activity is essential for Dictyostelium to grow on bacteria, its natural food substrate.

scholarly journals The Novel Avian Leukosis Virus Subgroup K Shares Its Cellular Receptor with Subgroup A

2019 ◽  
Vol 93 (17) ◽  
Author(s):  
David Přikryl ◽  
Jiří Plachý ◽  
Dana Kučerová ◽  
Anna Koslová ◽  
Markéta Reinišová ◽  
...  
Keyword(s):  
Host Range ◽  
Mammalian Cells ◽  
Ectopic Expression ◽  
Avian Leukosis Virus ◽  
Cell Surface Receptor ◽  
Genetic Ablation ◽  
Receptor Usage ◽  
Surface Receptor ◽  
Bona Fide ◽  
Avian Leukosis Virus Subgroup

ABSTRACTAvian leukosis virus subgroup K (ALV-K) is composed of newly emerging isolates, which, in sequence analyses, cluster separately from the well-characterized subgroups A, B, C, D, E, and J. However, it remains unclear whether ALV-K represents an independent ALV subgroup with regard to receptor usage, host range, and superinfection interference. In the present study, we examined the host range of the Chinese infectious isolate JS11C1, an ALV-K prototype, and we found substantial overlap of species that were either resistant or susceptible to ALV-A and JS11C1. Ectopic expression of the chickentvagene in mammalian cells conferred susceptibility to JS11C1, while genetic ablation of thetvagene rendered chicken DF-1 cells resistant to infection by JS11C1. Thus,tvaexpression is both sufficient and necessary for JS11C1 entry. Receptor sharing was also manifested in superinfection interference, with preinfection of cells with ALV-A, but not ALV-B or ALV-J, blocking subsequent JS11C1 infection. Finally, direct binding of JS11C1 and Tva was demonstrated by preincubation of the virus with soluble Tva, which substantially decreased viral infectivity in susceptible chicken cells. Collectively, these findings indicate that JS11C1 represents a new andbona fideALV subgroup that utilizes Tva for cell entry and binds to a site other than that for ALV-A.IMPORTANCEALV consists of several subgroups that are particularly characterized by their receptor usage, which subsequently dictates the host range and tropism of the virus. A few newly emerging and highly pathogenic Chinese ALV strains have recently been suggested to be an independent subgroup, ALV-K, based solely on their genomic sequences. Here, we performed a series of experiments with the ALV-K strain JS11C1, which showed its dependence on the Tva cell surface receptor. Due to the sharing of this receptor with ALV-A, both subgroups were able to interfere with superinfection. Because ALV-K could become an important pathogen and a significant threat to the poultry industry in Asia, the identification of a specific receptor could help in the breeding of resistant chicken lines with receptor variants with decreased susceptibility to the virus.

Protection of mammalian cells from diphtheria toxin by exogenous nucleotides

1979 ◽  
Vol 25 (3) ◽  
pp. 285-290 ◽  
Author(s):  
John L. Middlebrook ◽  
Rebecca B. Dorland
Keyword(s):  
Diphtheria Toxin ◽  
Mammalian Cells ◽  
Cell Surface Receptor ◽  
Lethal Effects ◽  
Cellular Protection ◽  
Future Studies ◽  
Degree Of Protection ◽  
Phosphate Chain ◽  
Surface Receptor ◽  
Toxin Receptor

Exogenous nucleotides were found to protect mammalian cells from the lethal effects of diphtheria toxin. Protective potency of a given nucleotide was base specific and phosphate chain length dependent. Full expression of protective potency required an intact nucleotide, but the effect did not appear to be mediated by nucleotide-induced phosphorylation. Nucleotides antagonized the binding of diphtheria toxin to its cell surface receptor in a manner that correlated with the degree of protection. It was concluded that cellular protection from diphtheria toxin by nucleotides results from inhibition of toxin–receptor binding and that nucleotides therefore may serve as valuable research tools for future studies.

scholarly journals A Dynamic Actin Cytoskeleton Functions at Multiple Stages of Clathrin-mediated Endocytosis

2005 ◽  
Vol 16 (2) ◽  
pp. 964-975 ◽  
Author(s):  
Defne Yarar ◽  
Clare M. Waterman-Storer ◽  
Sandra L. Schmid
Keyword(s):  
Cell Surface ◽  
Mammalian Cells ◽  
Actin Polymerization ◽  
Cell Surface Receptor ◽  
Actin Dynamics ◽  
Coated Vesicle ◽  
Vesicle Formation ◽  
Actin Assembly ◽  
Electron Microscopic ◽  
Surface Receptor

Clathrin-mediated endocytosis in mammalian cells is critical for a variety of cellular processes including nutrient uptake and cell surface receptor down-regulation. Despite the findings that numerous endocytic accessory proteins directly or indirectly regulate actin dynamics and that actin assembly is spatially and temporally coordinated with endocytosis, direct functional evidence for a role of actin during clathrin-coated vesicle formation is lacking. Here, we take parallel biochemical and microscopic approaches to address the contribution of actin polymerization/depolymerization dynamics to clathrin-mediated endocytosis. When measured using live-cell fluorescence microscopy, disruption of the F-actin assembly and disassembly cycle with latrunculin A or jasplakinolide results in near complete cessation of all aspects of clathrin-coated structure (CCS) dynamics. Stage-specific biochemical assays and quantitative fluorescence and electron microscopic analyses establish that F-actin dynamics are required for multiple distinct stages of clathrin-coated vesicle formation, including coated pit formation, constriction, and internalization. In addition, F-actin dynamics are required for observed diverse CCS behaviors, including splitting of CCSs from larger CCSs, merging of CCSs, and lateral mobility on the cell surface. Our results demonstrate a key role for actin during clathrin-mediated endocytosis in mammalian cells.

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