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The Journal of Clinical Investigation Oct 2023B cell clonal expansion and cerebrospinal fluid (CSF) oligoclonal IgG bands are established features of the immune response in multiple sclerosis (MS). Clone-specific...
B cell clonal expansion and cerebrospinal fluid (CSF) oligoclonal IgG bands are established features of the immune response in multiple sclerosis (MS). Clone-specific recombinant monoclonal IgG1 Abs (rAbs) derived from MS patient CSF plasmablasts bound to conformational proteolipid protein 1 (PLP1) membrane complexes and, when injected into mouse brain with human complement, recapitulated histologic features of MS pathology: oligodendrocyte cell loss, complement deposition, and CD68+ phagocyte infiltration. Conformational PLP1 membrane epitopes were complex and governed by the local cholesterol and glycolipid microenvironment. Abs against conformational PLP1 membrane complexes targeted multiple surface epitopes, were enriched within the CSF compartment, and were detected in most MS patients, but not in inflammatory and noninflammatory neurologic controls. CSF PLP1 complex Abs provide a pathogenic autoantibody biomarker specific for MS.
Topics: Mice; Animals; Humans; Multiple Sclerosis; Myelin Sheath; Immunoglobulin G; Epitopes; Proteolipids
PubMed: 37561592
DOI: 10.1172/JCI162731 -
Revue Scientifique Et Technique... Apr 2016There is a critical need in animal agriculture to develop novel antimicrobials and alternative strategies that will help to reduce the use of antibiotics and address the... (Review)
Review
There is a critical need in animal agriculture to develop novel antimicrobials and alternative strategies that will help to reduce the use of antibiotics and address the challenges of antimicrobial resistance. High-throughput gene expression analysis is providing new tools that are enabling the discovery of host-derived antimicrobial peptides. Examples of gene-encoded natural antibiotics that have gained attention include antimicrobial peptides such as human granulysin and its multi-species homolog, namely NK-lysin, which provide a protective response against a broad range of microbes and are a principal component of innate immunity in vertebrates. Both granulysin and NK-lysin are localised in cytolytic granules in natural killer and cytotoxic T lymphocytes. Host-derived NK-lysins that were first described in mammals are also found in avian species, and they have been shown to have antimicrobial activities that could potentially be used to control important poultry pathogens. Morphological alterations observed following chicken NK-lysin binding to Eimeria sporozoites and Escherichia coli membranes indicate damage and disruption of cell membranes, suggesting that NK-lysin kills pathogenic protozoans and bacteria by direct interaction. Genotype analysis revealed that chicken NK-lysin peptides derived from certain alleles were more effective at killing pathogens than those derived from others, which could potentially affect susceptibility to diseases. Although the host-derived antimicrobial peptides described in this paper may not, by themselves, be able to replace the antibiotics currently used in animal production, their use as specific treatments based on their known mechanisms of action is showing promising results.
Topics: Animals; Antimicrobial Cationic Peptides; Birds; Genomics; Proteolipids
PubMed: 27217171
DOI: 10.20506/rst.35.1.2420 -
Microbiology Spectrum Jan 2019Outer membrane vesicles (OMVs) are nanosized proteoliposomes derived from the outer membrane of Gram-negative bacteria. They are ubiquitously produced both in culture...
Outer membrane vesicles (OMVs) are nanosized proteoliposomes derived from the outer membrane of Gram-negative bacteria. They are ubiquitously produced both in culture and during infection and are now recognized to play crucial roles during host-microbe interactions. OMVs can transport a broad range of chemically diverse cargoes, including lipids and lipopolysaccharides, membrane-embedded and associated proteins and small molecules, peptidoglycan, and nucleic acids. Particularly, virulence factors such as adhesins and toxins are often enriched in OMVs. Here we discuss a variety of ways in which OMVs facilitate host-microbe interactions, including their contributions to biofilm formation, nutrient scavenging, and modulation of host cell function. We particularly examine recent findings regarding OMV-host cell interactions in the oral cavity and the gastrointestinal tract.
Topics: Bacterial Outer Membrane Proteins; Biological Transport; Cell Membrane; Gram-Negative Bacteria; Humans; Lipopolysaccharides; Proteolipids; Transport Vesicles
PubMed: 30681067
DOI: 10.1128/microbiolspec.PSIB-0001-2018 -
Trends in Endocrinology and Metabolism:... Dec 2016Skeletal muscle constitutes ∼40% of body mass and has the capacity to play a major role as thermogenic, metabolic, and endocrine organ. In addition to shivering,... (Review)
Review
Skeletal muscle constitutes ∼40% of body mass and has the capacity to play a major role as thermogenic, metabolic, and endocrine organ. In addition to shivering, muscle also contributes to nonshivering thermogenesis via futile sarcoplasmic/endoplasmic reticulum Ca ATPase (SERCA) activity. Sarcolipin (SLN), a regulator of SERCA activity in muscle, plays an important role in regulating muscle thermogenesis and metabolism. Uncoupling of SERCA by SLN increases ATP hydrolysis and heat production, and contributes to temperature homeostasis. SLN also affects whole-body metabolism and weight gain in mice, and is upregulated in various muscle diseases including muscular dystrophy, suggesting a role for SLN during increased metabolic demand. In this review we also highlight the physiological roles of skeletal muscle beyond contraction.
Topics: Animals; Humans; Muscle Proteins; Muscle, Skeletal; Proteolipids; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Thermogenesis
PubMed: 27637585
DOI: 10.1016/j.tem.2016.08.006 -
Chest Jun 1997
Review
Topics: Humans; Infant, Newborn; Lung; Lung Diseases; Proteolipids; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn
PubMed: 9184562
DOI: 10.1378/chest.111.6_supplement.129s-a -
Molekuliarnaia Biologiia 2021The mechanisms involved in the origin and development of malignant and neurodegenerative diseases are an important area of modern biomedicine. A crucial task is to...
The mechanisms involved in the origin and development of malignant and neurodegenerative diseases are an important area of modern biomedicine. A crucial task is to identify new molecular markers that are associated with rearrangements of intracellular signaling and can be used for prognosis and the development of effective treatment approaches. The proteolipid plasmolipin (PLLP) is a possible marker. PLLP is a main component of the myelin sheath and plays an important role in the development and normal function of the nervous system. PLLP is involved in intracellular transport, lipid raft formation, and Notch signaling. PLLP is presumably involved in various disorders, such as cancer, schizophrenia, Alzheimer's disease, and type 2 diabetes mellitus. PLLP and its homologs were identified as possible virus entry receptors. The review summarizes the data on the PLLP structure, normal functions, and role in diseases.
Topics: Diabetes Mellitus, Type 2; Humans; Myelin Sheath; Myelin and Lymphocyte-Associated Proteolipid Proteins; Nerve Tissue Proteins; Proteolipids
PubMed: 34837695
DOI: 10.31857/S0026898421060112 -
Biochimica Et Biophysica Acta Nov 1998Surfactant protein concentrations are precisely maintained during fetal development and postnatally controlled, at least in part, by the regulation of gene transcription... (Review)
Review
Surfactant protein concentrations are precisely maintained during fetal development and postnatally controlled, at least in part, by the regulation of gene transcription and/or mRNA stability. Together, these mechanisms contribute to the unique temporal-spatial distribution of surfactant protein synthesis that is characteristic of the mammalian lung. Surfactant proteins A, B and C are expressed primarily in subsets of respiratory epithelial cells, wherein their expression is modified by developmental, physiological, humoral and inflammatory stimuli. Cell specific and humoral regulation of surfactant protein transcription is determined by the interactions of a number of nuclear transcription proteins that function in combination, by binding to cis-acting elements located in the 5' regulatory regions of each of the surfactant protein genes. The unique combination of distinct and shared cis-acting elements and transcriptional proteins serves to modulate surfactant protein synthesis in the lung. The present review will summarize efforts to identify the mechanisms contributing to the regulation of surfactant protein gene transcription in the lung, focusing to the nuclear transcription factor, TTF-1 (or thyroid transcription factor-1), a member of the Nkchi2 family of nuclear transcription proteins. A complete review of regulatory aspects of surfactant homeostasis is beyond the scope of the present summary.
Topics: DNA-Binding Proteins; Gene Expression Regulation; Hepatocyte Nuclear Factor 3-beta; Lung; Nuclear Proteins; Proteolipids; Pulmonary Surfactants; Thyroid Nuclear Factor 1; Transcription Factors; Transcription, Genetic
PubMed: 9813380
DOI: 10.1016/s0925-4439(98)00076-3 -
Biochimica Et Biophysica Acta Nov 1998Mice lacking surfactant protein A (SP-A) mRNA and protein in vivo were generated using gene targeting techniques. SP-A (-/-) mice have normal levels of SP-B, SP-C and... (Review)
Review
Mice lacking surfactant protein A (SP-A) mRNA and protein in vivo were generated using gene targeting techniques. SP-A (-/-) mice have normal levels of SP-B, SP-C and SP-D mRNA and protein and survive and breed normally in vivarium conditions. Phospholipid composition, secretion and clearance, and incorporation of phospholipid precursors are normal in the SP-A (-/-) mice. Lungs of SP-A (-/-) mice have markedly decreased tubular myelin figures and clear Group B streptococci and Pseudomonas aeruginosa less efficiently than SP-A wild type mice. These studies of SP-A (-/-) mice demonstrate that SP-A has an important role in the innate immune system of the lung in vivo.
Topics: Animals; Bacteria; Gene Targeting; Immunity, Innate; Lung; Mice; Mice, Mutant Strains; Myelin Sheath; Phagocytosis; Proteolipids; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants
PubMed: 9813377
DOI: 10.1016/s0925-4439(98)00075-1 -
Plant Physiology Apr 2020Plasma membranes provide a highly selective environment for a large number of transmembrane and membrane-associated proteins. Whereas lateral movement of proteins in... (Review)
Review
Plasma membranes provide a highly selective environment for a large number of transmembrane and membrane-associated proteins. Whereas lateral movement of proteins in this lipid bilayer is possible, it is rather limited in turgid and cell wall-shielded plant cells. However, membrane-resident signaling processes occur on subsecond scales that cannot be explained by simple diffusion models. Accordingly, several receptors and other membrane-associated proteins are organized and functional in membrane nanodomains. Although the general presence of membrane nanodomains has become widely accepted as fact, fundamental functional aspects, the roles of individual lipid species and their interplay with proteins, and aspects of nanodomain maintenance and persistence remain poorly understood. Here, we review the current knowledge of nanodomain organization and function, with a particular focus on signaling processes involving proteins, lipids, and their interactions. Furthermore, we propose new and hypothetical aspects of plant membrane biology that we consider important for future research.
Topics: Cell Membrane; Membrane Microdomains; Models, Biological; Proteolipids; Signal Transduction
PubMed: 31857424
DOI: 10.1104/pp.19.01349 -
Journal of Structural Biology Oct 2009Planar model membranes, like supported lipid bilayers and surface-tethered vesicles, have been proven to be useful tools for the investigation of complex biological...
Planar model membranes, like supported lipid bilayers and surface-tethered vesicles, have been proven to be useful tools for the investigation of complex biological functions in a significantly less complex membrane environment. In this study, we introduce a supported double membrane system that should be useful for studies that target biological processes in the proximity of two lipid bilayers such as the periplasm of bacteria and mitochondria or the small cleft between pre- and postsynaptic neuronal membranes. Large unilamellar vesicles (LUV) were tethered to a preformed supported bilayer by a biotin-streptavidin tether. We show from single particle tracking (SPT) experiments that these vesicle are mobile above the plane of the supported membrane. At higher concentrations, the tethered vesicles fuse to form a second continuous bilayer on top of the supported bilayer. The distance between the two bilayers was determined by fluorescence interference contrast (FLIC) microscopy to be between 16 and 24nm. The lateral diffusion of labeled lipids in the second bilayer was very similar to that in supported membranes. SPT experiments with reconstituted syntaxin-1A show that the mobility of transmembrane proteins was not improved when compared with solid supported membranes.
Topics: Animals; Fluorescence Recovery After Photobleaching; Lipid Bilayers; Microscopy, Fluorescence; Proteolipids; Qa-SNARE Proteins; Rats
PubMed: 19236921
DOI: 10.1016/j.jsb.2009.02.008