scholarly journals Function of Protein S-Palmitoylation in Immunity and Immune-Related Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuqi Zhang ◽  
Ziran Qin ◽  
Wenhuan Sun ◽  
Feng Chu ◽  
Fangfang Zhou
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Mammalian Cells ◽  
Large Body ◽  
Protein S ◽  
Cellular Membrane ◽  
Immune Signaling ◽  
Substrate Protein ◽  
Associated Proteins ◽  
Immunologic Diseases

Protein S-palmitoylation is a covalent and reversible lipid modification that specifically targets cysteine residues within many eukaryotic proteins. In mammalian cells, the ubiquitous palmitoyltransferases (PATs) and serine hydrolases, including acyl protein thioesterases (APTs), catalyze the addition and removal of palmitate, respectively. The attachment of palmitoyl groups alters the membrane affinity of the substrate protein changing its subcellular localization, stability, and protein-protein interactions. Forty years of research has led to the understanding of the role of protein palmitoylation in significantly regulating protein function in a variety of biological processes. Recent global profiling of immune cells has identified a large body of S-palmitoylated immunity-associated proteins. Localization of many immune molecules to the cellular membrane is required for the proper activation of innate and adaptive immune signaling. Emerging evidence has unveiled the crucial roles that palmitoylation plays to immune function, especially in partitioning immune signaling proteins to the membrane as well as to lipid rafts. More importantly, aberrant PAT activity and fluctuations in palmitoylation levels are strongly correlated with human immunologic diseases, such as sensory incompetence or over-response to pathogens. Therefore, targeting palmitoylation is a novel therapeutic approach for treating human immunologic diseases. In this review, we discuss the role that palmitoylation plays in both immunity and immunologic diseases as well as the significant potential of targeting palmitoylation in disease treatment.

Tension-sensitive kinetochore phosphorylation in vitro

1998 ◽  
Vol 111 (21) ◽  
pp. 3189-3196 ◽  
Author(s):  
R.B. Nicklas ◽  
M.S. Campbell ◽  
S.C. Ward ◽  
G.J. Gorbsky
Keyword(s):  
Mammalian Cells ◽  
Chemical Change ◽  
Protein S ◽  
Living Cells ◽  
Mechanical Tension ◽  
In Vitro System ◽  
Substrate Protein ◽  
Meiotic Chromosomes ◽  
System A

Many cells have a checkpoint that detects a single misattached chromosome and delays anaphase, allowing time for error correction. Detection probably depends on tension-sensitive kinetochore protein phosphorylation. Somehow, mechanical tension, or some consequence of tension, produces a chemical change, dephosphorylation. The mechanism of tension-mediated dephosphorylation can be approached using an in vitro system. Earlier work showed that the kinetochores of washed chromosomes from a mammalian cell line can be phosphorylated in vitro simply by incubation with ATP and a phosphatase inhibitor. We confirm this for chromosomes from insect meiotic cells. Thus, kinetochores of washed chromosomes from diverse sources contain a complete phosphorylation system: a kinase, a phosphatase and the substrate protein(s). We show that phosphorylation in vitro is sensitive to tension, as it is in living cells. This makes the conditions required for phosphorylation in vitro relevant to the process in living cells. The phosphatase is ruled out as the tension-sensitive component in vitro, leaving either the kinase or the substrate as the sensitive component. We show that a kinase extracted from mammalian cells in mitosis phosphorylates the kinetochores of insect meiotic chromosomes very effectively. The mammalian kinase under-phosphorylates the kinetochore of the insect's X-chromosome, just as the native insect kinase does. This provides a clue to the evolution of a chromosome that is not detected by the checkpoint. The mammalian kinase is not tightly bound to the chromosome and thus functions primarily in solution. This suggests that the substrate's phosphorylatable groups are freely available to outside constituents, e.g. regulators, as well as to the kinetochore's own kinase and phosphatase.

scholarly journals A lipid-protein hybrid model for tight junction

2008 ◽  
Vol 295 (6) ◽  
pp. F1601-F1612 ◽  
Author(s):  
David B. N. Lee ◽  
Nora Jamgotchian ◽  
Suni G. Allen ◽  
Michael B. Abeles ◽  
Harry J. Ward
Keyword(s):  
Tight Junction ◽  
Hybrid Model ◽  
Protein Interactions ◽  
Large Body ◽  
Wide Acceptance ◽  
Associated Proteins ◽  
Epithelial Tight Junction ◽  
Lipid Protein Interactions ◽  
And Function ◽  
Adjoining Cell

The epithelial tight junction (TJ) was first described ultrastructurally as a fusion of the outer lipid leaflets of the adjoining cell membrane bilayers (hemifusion). The discovery of an increasing number of integral TJ and TJ-associated proteins has eclipsed the original lipid-based model with the wide acceptance of a protein-centric model for the TJ. In this review, we stress the importance of lipids in TJ structure and function. A lipid-protein hybrid model accommodates a large body of information supporting the lipidic characteristics of the TJ, harmonizes with the accumulating evidence supporting the TJ as an assembly of lipid rafts, and focuses on an important, but relatively unexplored, field of lipid-protein interactions in the morphology, physiology, and pathophysiology of the TJ.

scholarly journals DNA-Encircled Lipid Bilayers

2018 ◽  
Author(s):  
Katarina Iric ◽  
Madhumalar Subramanian ◽  
Jana Oertel ◽  
Nayan P. Agarwal ◽  
Michael Matthies ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Protein Interactions ◽  
Protein Function ◽  
Dna Nanotechnology ◽  
Lipid Vesicles ◽  
Associated Proteins

ABSTRACTLipid bilayers and lipid-associated proteins play a crucial role in biology. As in vivo studies and manipulation are inherently difficult, several membrane-mimetic systems have been developed to enable investigation of lipidic phases, lipid-protein interactions, membrane protein function and membrane structure in vitro. Controlling the size and shape, or site-specific functionalization is, however, difficult to achieve with established membrane mimetics based on membrane scaffolding proteins, polymers or peptides. In this work, we describe a route to leverage the unique programmability of DNA nanotechnology and create DNA-encircled bilayers (DEBs), which are made of multiple copies of an alkylated oligonucleotide hybridized to a single-stranded minicircle. To stabilize the hydrophobic rim of the lipid bilayer, and to prevent formation of lipid vesicles, we introduced up to 2 alkyl chains per helical that point to the inside of the toroidal DNA ring and interact with the hydrophobic side chains of the encapsulated lipid bilayer. The DEB approach described herein provides unprecedented control of size, and allows the orthogonal functionalizations and arrangement of engineered membrane nanoparticles and will become a valuable tool for biophysical investigation of lipid phases and lipid-associated proteins and complexes including structure determination of membrane proteins and pharmacological screenings of membrane proteins.

SUMO in the mammalian response to DNA damage

2010 ◽  
Vol 38 (1) ◽  
pp. 92-97 ◽  
Author(s):  
Joanna R. Morris
Keyword(s):  
Dna Damage ◽  
Protein Interactions ◽  
Protein Function ◽  
Mammalian Cells ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
Genotoxic Stress ◽  
Breast Cancer Susceptibility ◽  
Model Organisms ◽  
Breast Cancer Susceptibility Gene

Modification by SUMOs (small ubiquitin-related modifiers) is largely transient and considered to alter protein function through altered protein–protein interactions. These modifications are significant regulators of the response to DNA damage in eukaryotic model organisms and SUMOylation affects a large number of proteins in mammalian cells, including several proteins involved in the response to genomic lesions [Golebiowski, Matic, Tatham, Cole, Yin, Nakamura, Cox, Barton, Mann and Hay (2009) Sci. Signaling 2, ra24]. Furthermore, recent work [Morris, Boutell, Keppler, Densham, Weekes, Alamshah, Butler, Galanty, Pangon, Kiuchi, Ng and Solomon (2009) Nature 462, 886–890; Galanty, Belotserkovskaya, Coates, Polo, Miller and Jackson (2009) Nature 462, 935–939] has revealed the involvement of the SUMO cascade in the BRCA1 (breast-cancer susceptibility gene 1) pathway response after DNA damage. The present review examines roles described for the SUMO pathway in the way mammalian cells respond to genotoxic stress.

scholarly journals Regulation of Dynamic Protein S-Acylation

2021 ◽  
Vol 8 ◽  
Author(s):  
Jessica J. Chen ◽  
Ying Fan ◽  
Darren Boehning
Keyword(s):  
Fatty Acids ◽  
Protein Interactions ◽  
Protein Function ◽  
Protein S ◽  
Cell Types ◽  
Cysteine Residues ◽  
Substrate Selection ◽  
Enzymatic Regulation ◽  
Reversible Addition ◽  
Neurological Conditions

Protein S-acylation is the reversible addition of fatty acids to the cysteine residues of target proteins. It regulates multiple aspects of protein function, including the localization to membranes, intracellular trafficking, protein interactions, protein stability, and protein conformation. This process is regulated by palmitoyl acyltransferases that have the conserved amino acid sequence DHHC at their active site. Although they have conserved catalytic cores, DHHC enzymes vary in their protein substrate selection, lipid substrate preference, and regulatory mechanisms. Alterations in DHHC enzyme function are associated with many human diseases, including cancers and neurological conditions. The removal of fatty acids from acylated cysteine residues is catalyzed by acyl protein thioesterases. Notably, S-acylation is now known to be a highly dynamic process, and plays crucial roles in signaling transduction in various cell types. In this review, we will explore the recent findings on protein S-acylation, the enzymatic regulation of this process, and discuss examples of dynamic S-acylation.

scholarly journals Mechanisms of Spindle Positioning: Lessons from Worms and Mammalian Cells

Biomolecules ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 80 ◽  
Author(s):  
Sachin Kotak
Keyword(s):  
Cell Fate ◽  
Protein Interactions ◽  
Mitotic Spindle ◽  
Mammalian Cells ◽  
Physical Nature ◽  
Cell Cortex ◽  
Protein Protein Interactions ◽  
Spindle Positioning ◽  
Cellular Environment ◽  
Associated Proteins

Proper positioning of the mitotic spindle is fundamental for specifying the site for cleavage furrow, and thus regulates the appropriate sizes and accurate distribution of the cell fate determinants in the resulting daughter cells during development and in the stem cells. The past couple of years have witnessed tremendous work accomplished in the area of spindle positioning, and this has led to the emergence of a working model unravelling in-depth mechanistic insight of the underlying process orchestrating spindle positioning. It is evident now that the correct positioning of the mitotic spindle is not only guided by the chemical cues (protein–protein interactions) but also influenced by the physical nature of the cellular environment. In metazoans, the key players that regulate proper spindle positioning are the actin-rich cell cortex and associated proteins, the ternary complex (Gα/GPR-1/2/LIN-5 in Caenorhabditis elegans, Gαi/Pins/Mud in Drosophila and Gαi1-3/LGN/NuMA in humans), minus-end-directed motor protein dynein and the cortical machinery containing myosin. In this review, I will mainly discuss how the abovementioned components precisely and spatiotemporally regulate spindle positioning by sensing the physicochemical environment for execution of flawless mitosis.

Involvement of Glycolipid-Enriched Domains in the Transduction Mechanism of Neurotrophins in Cultured Neurons

1999 ◽  
Vol 19 (5) ◽  
pp. 385-395 ◽  
Author(s):  
P. Palestini ◽  
M. Masserini ◽  
G. Bottiroli ◽  
J. Brunner ◽  
T. Mutoh ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Large Body ◽  
Protein Composition ◽  
Membrane Structures ◽  
Associated Proteins ◽  
Dynamic Structures ◽  
Related Proteins

Specialized domains, displaying a peculiar lipid and protein composition, are present within the plasma membrane of mammalian cells and play a pivotal role in fundamental membrane-associated events. Among lipids, sphingolipids (in particular glycolipids and sphingomyelin) are characteristically enriched within such domains. Moreover, a series of functionally related proteins is present, suggesting the involvement of these membrane structures in the mechanism of signal transduction and lipid/protein sorting. An increasing body of evidence suggests that domains are dynamic structures, and that their dynamic fluctuations can modulate the activity of domain-associated proteins through changes of glycolipid–protein interaction. Even if a large body of experimental investigation has been carried out on eukaryotic cells, only little attention has been paid to the neuron. The purpose of the present review is to summarize the observations implying a functional role of glycolipid-enriched domains in cultured rat cerebellar granule cells.

scholarly journals Protein S -palmitoylation in immunity

Open Biology ◽  
2021 ◽  
Vol 11 (3) ◽  
Author(s):  
Tandrila Das ◽  
Jacob S. Yount ◽  
Howard C. Hang
Keyword(s):  
Immune Responses ◽  
Protein Interactions ◽  
Immune Cells ◽  
Protein S ◽  
Lipid Modification ◽  
Protein Protein Interactions ◽  
Protein Activity ◽  
Dynamic Regulation ◽  
Targeted Analysis ◽  
Associated Proteins

S -palmitoylation is a reversible posttranslational lipid modification of proteins. It controls protein activity, stability, trafficking and protein–protein interactions. Recent global profiling of immune cells and targeted analysis have identified many S -palmitoylated immunity-associated proteins. Here, we review S -palmitoylated immune receptors and effectors, and their dynamic regulation at cellular membranes to generate specific and balanced immune responses. We also highlight how this understanding can drive therapeutic advances to pharmacologically modulate immune responses.

Characterization of microtubules by dark-field STEM and replication

1991 ◽  
Vol 49 ◽  
pp. 152-153
Author(s):  
S.B. Andrews ◽  
R.D. Leapman ◽  
P.E. Gallant ◽  
T.S. Reese
Keyword(s):  
Protein Interactions ◽  
Low Dose ◽  
Unit Length ◽  
Dark Field ◽  
Carbon Films ◽  
Microtubule Associated Proteins ◽  
Molecular Weights ◽  
Freeze Dried ◽  
Protein Motors ◽  
Associated Proteins

As part of a study on protein interactions involved in microtubule (MT)-based transport, we used the VG HB501 field-emission STEM to obtain low-dose dark-field mass maps of isolated, taxol-stabilized MTs and correlated these micrographs with detailed stereo images from replicas of the same MTs. This approach promises to be useful for determining how protein motors interact with MTs. MTs prepared from bovine and squid brain tubulin were purified and free from microtubule-associated proteins (MAPs). These MTs (0.1-1 mg/ml tubulin) were adsorbed to 3-nm evaporated carbon films supported over Formvar nets on 600-m copper grids. Following adsorption, the grids were washed twice in buffer and then in either distilled water or in isotonic or hypotonic ammonium acetate, blotted, and plunge-frozen in ethane/propane cryogen (ca. -185 C). After cryotransfer into the STEM, specimens were freeze-dried and recooled to ca.-160 C for low-dose (<3000 e/nm2) dark-field mapping. The molecular weights per unit length of MT were determined relative to tobacco mosaic virus standards from elastic scattering intensities. Parallel grids were freeze-dried and rotary shadowed with Pt/C at 14°.

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