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Histology and Histopathology Jul 2004Polarized transport of lipids and proteins to the apical and basolateral membrane subdomains is essential for the functioning of epithelial cells. Apical transport is... (Review)
Review
Polarized transport of lipids and proteins to the apical and basolateral membrane subdomains is essential for the functioning of epithelial cells. Apical transport is mediated by a direct route from the Golgi and an indirect route, referred to as transcytosis, involving the transport of the protein to the basolateral membrane followed by its internalization and subsequent transcellular transport to the apical subdomain. MAL and MAL2 have been demonstrated to be essential components of the machinery for the direct and indirect routes, respectively. Herein, we review the range of expression of MAL and MAL2 in normal human tissue and compare it with that of neoplastic tissue. Our analysis provides insight into the potential use of MAL- and MAL2-mediated pathways in many types of epithelial cells as well as in nonepithelial cells. In addition, the specific alterations in MAL and/or MAL2 expression observed in specific types of carcinoma provides a basis to understand the loss of the polarized phenotype that frequently accompanies the neoplastic transformation process. This points out potential applications of MAL and MAL2 as markers for tumor characterization.
Topics: Cell Polarity; Epithelial Cells; Humans; Membrane Microdomains; Membrane Transport Proteins; Models, Biological; Myelin Proteins; Myelin and Lymphocyte-Associated Proteolipid Proteins; Neoplasms; Protein Transport; Proteolipids; Tissue Distribution; Vesicular Transport Proteins
PubMed: 15168355
DOI: 10.14670/HH-19.925 -
Nature Materials Sep 2016A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of...
A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of biological barriers that limit their optimal biodistribution. Bioinspired drug-delivery carriers formulated by bottom-up or top-down strategies have emerged as an alternative approach to evade the mononuclear phagocytic system and facilitate transport across the endothelial vessel wall. Here, we describe a method that leverages the advantages of bottom-up and top-down strategies to incorporate proteins derived from the leukocyte plasma membrane into lipid nanoparticles. The resulting proteolipid vesicles-which we refer to as leukosomes-retained the versatility and physicochemical properties typical of liposomal formulations, preferentially targeted inflamed vasculature, enabled the selective and effective delivery of dexamethasone to inflamed tissues, and reduced phlogosis in a localized model of inflammation.
Topics: Biomimetic Materials; Drug Carriers; Inflammation; Leukocytes; Membrane Proteins; Proteolipids
PubMed: 27213956
DOI: 10.1038/nmat4644 -
The American Journal of Physiology Feb 1995In the short span of ten years, our understanding of human surfactant-associated protein A (SP-A) has advanced rapidly at both the level of the protein and the level of... (Review)
Review
In the short span of ten years, our understanding of human surfactant-associated protein A (SP-A) has advanced rapidly at both the level of the protein and the level of the gene. In the period 1984-1988, the protein was biochemically characterized and two SP-A precursors were identified. The molecular characterization was begun with the publication of an SP-A genomic sequence and sequences of two SP-A cDNAs, suggesting the presence of two SP-A genes. In the period 1991-1992, an SP-A pseudogene, a second SP-A genomic sequence, and an SP-A allelic variant were described. Since that time, a picture of increasing complexity has emerged from studies of the two SP-A genes. This complexity includes alternative splicing of 5' untranslated exons, allelic variants of both SP-A genes, and sequence heterogeneity within the 3' untranslated region. The challenge for the future will be to discover the physiological significance of the genetic complexity of human SP-A.
Topics: Alleles; Animals; Genes; Genetic Variation; Genome; Glycoproteins; Humans; Physiology; Proteolipids; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants
PubMed: 7864137
DOI: 10.1152/ajplung.1995.268.2.L162 -
Progress in Neurobiology Apr 2000The myelin and lymphocyte protein MAL (VIP17/MVP17) is a proteolipid of 17 kD with a hydrophobicity pattern that indicates a four transmembrane domain structure. The MAL... (Review)
Review
The myelin and lymphocyte protein MAL (VIP17/MVP17) is a proteolipid of 17 kD with a hydrophobicity pattern that indicates a four transmembrane domain structure. The MAL cDNA has been cloned from human T-cells, rat oligodendrocytes and the Madin-Darby canine kidney (MDCK) cell line. In the nervous system both myelinating cells, oligodendrocytes and Schwann cells, express MAL protein. MAL expression parallels myelin formation, and MAL is predominantly localized in compact myelin. Prior to myelin formation MAL is also found in immature Schwann cells. Outside the nervous system MAL expression is found in T-cells and in distinct epithelial cells, e.g. in kidney, stomach and thyroid gland, where MAL is localised in the apical plasma membrane. Specific glycosphingolipids, e.g. galactosylceramide and sulfatide, are enriched in such apical kidney and stomach membranes as well as in myelin. MAL copurifies with these glycosphingolipids in detergent insoluble domains, indicating a close association and possible functional interactions of MAL with glycosphingolipids in these tissues. Moreover, recent reports point to additional functions of MAL-glycosphingolipid complexes in signalling, cell differentiation and apical sorting. The role of MAL in the formation, stabilisation and maintenance of glycosphingolipid-enriched membrane microdomains and its contribution to specific membrane properties in myelin and epithelial cells are discussed.
Topics: Amino Acid Sequence; Animals; Glycosphingolipids; Humans; Immune System; Membrane Transport Proteins; Molecular Conformation; Molecular Sequence Data; Multigene Family; Myelin Proteins; Myelin Sheath; Myelin and Lymphocyte-Associated Proteolipid Proteins; Proteolipids
PubMed: 10739088
DOI: 10.1016/s0301-0082(99)00039-8 -
American Journal of Respiratory Cell... Aug 1998The surfactant-associated proteins SP-A and SP-D are members of a family of collagenous host defense lectins, designated collectins. There is increasing evidence that... (Review)
Review
The surfactant-associated proteins SP-A and SP-D are members of a family of collagenous host defense lectins, designated collectins. There is increasing evidence that these pulmonary epithelial-derived proteins are important components of the innate immune response to microbial challenge, and that they participate in other aspects of immune and inflammatory regulation within the lung. The collectins bind to glycoconjugates and/or lipid moieties expressed by a wide variety of microorganisms and certain other organic particles in vitro. Although binding may facilitate microbial clearance through aggregation or other direct effects on the organism, SP-A and SP-D also have the capacity to modulate leukocyte function and, in some circumstances, to enhance their killing of microorganisms. The biologic activity of cell wall components, such as gram-negative bacterial polysaccharides, may be altered by interactions with collectins. Complementary or cooperative interactions between SP-A and SP-D could contribute to the efficiency of this defense system. Collectins may play particularly important roles in settings of inadequate or impaired specific immunity. Acquired or genetic alterations in the levels of active proteins within the airspaces and distal airways may increase susceptibility to infection.
Topics: Animals; Glycoproteins; Humans; Lung; Lung Diseases; Protein Binding; Proteolipids; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Protein D; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants
PubMed: 9698590
DOI: 10.1165/ajrcmb.19.2.140 -
Seminars in Perinatology Jul 1988In summary, the isolation and characterization of three surfactant proteins have considerably changed our understanding of the nature of pulmonary surfactant and its... (Review)
Review
In summary, the isolation and characterization of three surfactant proteins have considerably changed our understanding of the nature of pulmonary surfactant and its metabolism. The isolation of the cDNAs and genes encoding the proteins and the elucidation of their structure now makes possible the generation of surfactant proteins for further study and for therapy of surfactant deficient states. Artificial surfactant consisting of appropriately modified human proteins can be produced by recombinant DNA technology. Mixed with appropriate synthetic phospholipids, these proteins may be useful for the treatment of infants with hyaline membrane disease. Significant progress has been made in identifying and characterizing these three more abundant proteins; however, many questions regarding the functions of numerous other proteins present in surfactant (whether produced by Type II cells, Type I cell, Clara cell, or others) remain unanswered. Knowledge of the factors controlling developmental expression of surfactant phospholipids and protein as well as the molecular basis of the interactions among the surfactant proteins and phospholipids may lead to new strategies for therapy of hyaline membrane disease. Major questions regarding the site and nature of posttranslational modification of the surfactant proteins, their sites of assembly with lipids, and their precise roles in the metabolism of surfactant in vitro remain to be clarified. It is hoped that answers to these questions will facilitate the identification and design of appropriate therapy of infants and adults with pulmonary disease associated with surfactant deficiency.
Topics: Animals; DNA; Genes; Glycoproteins; Humans; Proteolipids; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants
PubMed: 3041604
DOI: No ID Found -
Zhurnal Evoliutsionnoi Biokhimii I... 1986Proteolipid complex of Folch-Lees has been obtained and purified from the myelin and synaptosomes of the brain of the frog Rana temporaria and hen Gallus domesticus.... (Comparative Study)
Comparative Study
Proteolipid complex of Folch-Lees has been obtained and purified from the myelin and synaptosomes of the brain of the frog Rana temporaria and hen Gallus domesticus. Relative content of this proteolipid and glycolipids in the myelin is almost twice higher, whereas that of phospholipids--1 1/2 times lower than in the synaptosomal membranes of the same animal. Protein content of this complex is higher for myelin than for synaptosomal membranes; opposite relation was found with respect to phospholipid content. Within this complex, lipids are presented mainly by phospholipids, especially by acid ones which amount to 30-60%. Proteolipid complexes fro the myelin and synaptosomes differ from each other by their lipid component. Myelin proteolipid complex contains mainly phosphatidylserine and phosphatid acid, whereas synaptosomal one--phosphatidylserine and diphosphatediglycerol. No significant differences were found in fatty acid composition of phospholipids from proteolipid complex from myelin and synaptosomes as compared to this composition in the initial membranes.
Topics: Animals; Brain; Chickens; Fatty Acids; Female; Lipids; Myelin Sheath; Phospholipids; Proteolipids; Rana temporaria; Synaptosomes
PubMed: 3490079
DOI: No ID Found -
Annals of the New York Academy of... Sep 1999CMT polyneuropathy is a complex genetically and clinically heterogeneous group of disorders. The rapid advances in our understanding of the molecular basis of these... (Review)
Review
CMT polyneuropathy is a complex genetically and clinically heterogeneous group of disorders. The rapid advances in our understanding of the molecular basis of these groups of neuropathies have helped to resolve some of the controversial issues regarding the clinical and genetic classification. However, there is still confusion and chaos in the terminology employed by different groups of researchers. A reclassification based on the molecular mechanisms of these neuropathies will help in the future to unify and simplify the diagnosis of these complex disorders. The understanding of the molecular mechanisms will also help in the future to find a way to control or treat these hereditary neuropathies.
Topics: Charcot-Marie-Tooth Disease; Connexins; Gene Duplication; Humans; Membrane Proteins; Myelin and Lymphocyte-Associated Proteolipid Proteins; Nerve Tissue Proteins; Proteolipids
PubMed: 10586233
DOI: No ID Found -
Neurochemical Research Mar 1998This review is a personal memoir of the history of proteolipids and is limited to aspects of the field with which the author has been involved in one way or another. The...
This review is a personal memoir of the history of proteolipids and is limited to aspects of the field with which the author has been involved in one way or another. The discovery of proteolipids was a serendipitous observation made in the course of the study of sulfatides. Initial focus was on the chemical characterization of brain proteolipids, their behavior under different conditions and their identification as the major protein of CNS myelin. The sequence of PLP was obtained using solid phase protein sequencing techniques. This, in turn, made possible a new era in which biochemical, cellular and molecular approaches could be applied to address new questions about PLP. Identification of genetic defects in the PLP molecule and its regulation has contributed to understanding myelin biology. Studies of the encephalitogenic activity of PLP in animal models have influenced the views of inflammatory processes in multiple sclerosis. Despite remarkable progress, much remains to be learned about the structure and function of PLP.
Topics: Animals; History, 20th Century; Humans; Proteolipids; United States
PubMed: 9482238
DOI: 10.1023/a:1022488912996 -
Biochimie May 1986A combination of lipophilic gel permeation chromatography and ion-exchange chromatography in organic solvents was used to purify low molecular weight proteolipids from...
A combination of lipophilic gel permeation chromatography and ion-exchange chromatography in organic solvents was used to purify low molecular weight proteolipids from bovine brain. Cleavage peptides were purified by HPLC and studied mainly by the fast atom bombardment--mass spectrometry technique. A proteolipid of Mr 14 000 contains several peptides from the first 113 amino acids of the major myelin proteolipid (MMPL) plus an extra unknown blocked N-terminal peptide. A proteolipid of Mr 16 000 contains smaller peptides belonging to a C-terminal fragment of MMPL of about 160 residues. These two proteolipids do not seem to be artifacts from MMPL.
Topics: Amino Acids; Animals; Brain Chemistry; Cattle; Chromatography, Gel; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Cyanogen Bromide; Mass Spectrometry; Molecular Weight; Peptide Fragments; Proteolipids; Trypsin
PubMed: 3089328
DOI: 10.1016/s0300-9084(86)80161-4