Browsing by Subject "Cell membrane"

Now showing 1 - 5 of 5
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    Cell-surface Milieu Remodeling in Human Dendritic Cell Activation
    (The American Association of Immunologists, 2024) Udeshi, Namrata D.; Xu, Charles; Jiang, Zuzhi; Gao, Shihong Max; Yin, Qian; Luo, Wei; Carr, Steven A.; Davis, Mark M.; Li, Jiefu; Microbiology and Immunology, School of Medicine
    Dendritic cells (DCs) are specialized sentinel and APCs coordinating innate and adaptive immunity. Through proteins on their cell surface, DCs sense changes in the environment, internalize pathogens, present processed Ags, and communicate with other immune cells. By combining chemical labeling and quantitative mass spectrometry, we systematically profiled and compared the cell-surface proteomes of human primary conventional DCs (cDCs) in their resting and activated states. TLR activation by a lipopeptide globally reshaped the cell-surface proteome of cDCs, with >100 proteins upregulated or downregulated. By simultaneously elevating positive regulators and reducing inhibitory signals across multiple protein families, the remodeling creates a cell-surface milieu promoting immune responses. Still, cDCs maintain the stimulatory-to-inhibitory balance by leveraging a distinct set of inhibitory molecules. This analysis thus uncovers the molecular complexity and plasticity of the cDC cell surface and provides a roadmap for understanding cDC activation and signaling.
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    Distinctive Subcellular Inhibition of Cytokine-Induced Src by Salubrinal and Fluid Flow
    (Public Library of Science, 2014-08-26) Wan, Qiaoqiao; Xu, Wenxiao; Yan, Jing-long; Yokota, Hiroki; Na, Sungsoo; Anatomy, Cell Biology and Physiology, School of Medicine
    A non-receptor protein kinase Src plays a crucial role in fundamental cell functions such as proliferation, migration, and differentiation. While inhibition of Src is reported to contribute to chondrocyte homeostasis, its regulation at a subcellular level by chemical inhibitors and mechanical stimulation has not been fully understood. In response to inflammatory cytokines and stress to the endoplasmic reticulum (ER) that increase proteolytic activities in chondrocytes, we addressed two questions: Do cytokines such as interleukin 1 beta (IL1β) and tumor necrosis factor alpha (TNFα) induce location-dependent Src activation? Can cytokine-induced Src activation be suppressed by chemically alleviating ER stress or by applying fluid flow? Using live cell imaging with two Src biosensors (i.e., cytosolic, and plasma membrane-bound biosensors) for a fluorescence resonance energy transfer (FRET) technique, we determined cytosolic Src activity as well as membrane-bound Src activity in C28/I2 human chondrocytes. In response to TNFα and IL1β, both cytosolic and plasma membrane-bound Src proteins were activated, but activation in the cytosol occurred earlier than that in the plasma membrane. Treatment with salubrinal or guanabenz, two chemical agents that attenuate ER stress, significantly decreased cytokine-induced Src activities in the cytosol, but not in the plasma membrane. In contrast, fluid flow reduced Src activities in the plasma membrane, but not in the cytosol. Collectively, the results demonstrate that Src activity is differentially regulated by salubrinal/guanabenz and fluid flow in the cytosol and plasma membrane.
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    Elastic Properties of Polyunsaturated Phosphatidylethanolamines Influence Rhodopsin Function
    (Royal Society of Chemistry, 2013) Teague, Walter E., Jr.; Soubias, Olivier; Petrache, Horia; Fuller, Nola; Hines, Kirk G.; Rand, R. Peter; Gawrisch, Klaus; Physics, School of Science
    Membranes with a high content of polyunsaturated phosphatidylethanolamines (PE) facilitate formation of metarhodopsin-II (M(II)), the photointermediate of bovine rhodopsin that activates the G protein transducin. We determined whether M(II)-formation is quantitatively linked to the elastic properties of PEs. Curvature elasticity of monolayers of the polyunsaturated lipids 18 : 0-22 : 6(n - 3)PE, 18 : 0-22 : 5(n)- 6PE and the model lipid 18 : 1(n - 9)-18 : 1,(n- 9)PE were investigated in the inverse hexagonal phase. All three lipids form lipid monolayers with rather low spontaneous radii of curvature of 26-28 angstroms. In membranes, all three PEs generate high negative curvature elastic stress that shifts the equilibrium of MI(I)/M(II) photointermediates of rhodopsin towards M(II) formation.
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    Forming a Complex with MHC Class I Molecules Interferes with Mouse CD1d Functional Expression
    (Public Library of Science, 2013-08-29) Gourapura, Renukaradhya J.; Khan, Masood A.; Gallo, Richard M.; Shaji, Daniel; Liu, Jianyun; Brutkiewicz, Randy R.; Microbiology and Immunology, School of Medicine
    CD1d molecules are structurally similar to MHC class I, but present lipid antigens as opposed to peptides. Here, we show that MHC class I molecules physically associate with (and regulate the functional expression of) mouse CD1d on the surface of cells. Low pH (3.0) acid stripping of MHC class I molecules resulted in increased surface expression of murine CD1d on antigen presenting cells as well as augmented CD1d-mediated antigen presentation to NKT cells. Consistent with the above results, TAP1-/- mice were found to have a higher percentage of type I NKT cells as compared to wild type mice. Moreover, bone marrow-derived dendritic cells from TAP1-/- mice showed increased antigen presentation by CD1d compared to wild type mice. Together, these results suggest that MHC class I molecules can regulate NKT cell function, in part, by masking CD1d.
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    PDZ proteins SCRIB and DLG1 regulate myeloma cell surface CD86 expression, growth, and survival
    (American Association for Cancer Research, 2022) Moser-Katz, Tyler; Gavile, Catherine M.; Barwick, Benjamin G.; Lee, Kelvin P.; Boise, Lawrence H.; Medicine, School of Medicine
    Despite advances in the treatment of multiple myeloma in the past decades, the disease remains incurable, and understanding signals and molecules that can control myeloma growth and survival are important for the development of novel therapeutic strategies. One such molecule, CD86, regulates multiple myeloma cell survival via its interaction with CD28 and signaling through its cytoplasmic tail. Although the CD86 cytoplasmic tail has been shown to be involved in drug resistance and can induce molecular changes in multiple myeloma cells, its function has been largely unexplored. Here, we show that CD86 cytoplasmic tail has a role in trafficking CD86 to the cell surface. This is due in part to a PDZ-binding motif at its C-terminus which is important for proper trafficking from the Golgi apparatus. BioID analysis revealed 10 PDZ domain-containing proteins proximal to CD86 cytoplasmic tail in myeloma cells. Among them, we found the planar cell polarity proteins, SCRIB and DLG1, are important for proper CD86 surface expression and the growth and survival of myeloma cells. These findings indicate a mechanism by which myeloma cells confer cellular survival and drug resistance and indicate a possible motif to target for therapeutic gain.