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Heparan
Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (HSPG, i.e. Heparan Sulfate ProteoGlycan) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligands, including Wnt, and regulates a wide range of biological activities, including developmental processes, angiogenesis, blood coagulation, abolishing detachment activity by GrB (Granzyme B), and tumour metastasis. HS has also been shown to serve as cellular receptor for a number of viruses, including the respiratory syncytial virus. One study suggests that cellular heparan sulfate has a role in SARS-CoV-2 Infection, particularly when the virus attaches with ACE2. Proteoglycans The major cell membrane HSPGs are the transmembrane syndecans and the glycosylphosphatidylinositol (GPI) anchored glypicans. Other minor forms of membrane HSPG include betaglycan and the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Perlecan
Perlecan (PLC) also known as basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) or heparan sulfate proteoglycan 2 (HSPG2), is a protein that in humans is encoded by the ''HSPG2'' gene. The HSPG2 gene codes for a 4,391 amino acid protein with a molecular weight of 468,829. It is one of the largest known proteins. Perlecan was originally isolated from a tumor cell line and shown to be present in all native basement membranes. Perlecan is a large multidomain (five domains, labeled I-V) proteoglycan that binds to and cross-links many extracellular matrix (ECM) components and cell-surface molecules. Perlecan is synthesized by both vascular endothelial and smooth muscle cells and deposited in the extracellular matrix of parahoxozoans. Perlecan is highly conserved across species and the available data indicate that it has evolved from ancient ancestors by gene duplication and exon shuffling. Structure Perlecan consists of a core protein of molecular weight 4 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Heparan Sulfate
Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (HSPG, i.e. Heparan Sulfate ProteoGlycan) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligands, including Wnt, and regulates a wide range of biological activities, including developmental processes, angiogenesis, blood coagulation, abolishing detachment activity by GrB (Granzyme B), and tumour metastasis. HS has also been shown to serve as cellular receptor for a number of viruses, including the respiratory syncytial virus. One study suggests that cellular heparan sulfate has a role in SARS-CoV-2 Infection, particularly when the virus attaches with ACE2. Proteoglycans The major cell membrane HSPGs are the transmembrane syndecans and the glycosylphosphatidylinositol (GPI) anchored glypicans. Other minor forms of membrane HSPG include betaglycan and the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Syndecans
Syndecans are single transmembrane domain proteins that are thought to act as coreceptors, especially for G protein-coupled receptors. More specifically, these core proteins carry three to five heparan sulfate and chondroitin sulfate chains, i.e. they are proteoglycans, which allow for interaction with a large variety of ligands including fibroblast growth factors, vascular endothelial growth factor, transforming growth factor-beta, fibronectin and antithrombin-1. Interactions between fibronectin and some syndecans can be modulated by the extracellular matrix protein tenascin C. Family members and Structure The syndecan protein family has four members. Syndecans 1 and 3 and syndecans 2 and 4, making up separate subfamilies, arose by gene duplication and divergent evolution from a single ancestral gene. The syndecan numbers reflect the order in which the cDNAs for each family member were cloned. All syndecans have an N-terminal signal peptide, an ectodomain, a single hydroph ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glypicans
Glypicans constitute one of the two major families of heparan sulfate proteoglycans, with the other major family being syndecans. Six glypicans have been identified in mammals, and are referred to as GPC1 through GPC6. In ''Drosophila'' two glypicans have been identified, and these are referred to as dally (division abnormally delayed) and dally-like. One glypican has been identified in ''C. elegans''. Glypicans seem to play a vital role in developmental morphogenesis, and have been suggested as regulators for the Wnt and Hedgehog cell signaling pathways. They have additionally been suggested as regulators for fibroblast growth factor and bone morphogenic protein signaling. Structure While six glypicans have been identified in mammals, several characteristics remain consistent between these different proteins. First, the core protein of all glypicans is similar in size, approximately ranging between 60 and 70 kDa. Additionally, in terms of amino acid sequence, the location of fo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Heparin
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatment of heart attacks and unstable angina. It is given intravenously or by injection under the skin. Other uses for its anticoagulant properties include inside blood specimen test tubes and kidney dialysis machines. Common side effects include bleeding, pain at the injection site, and low blood platelets. Serious side effects include heparin-induced thrombocytopenia. Greater care is needed in those with poor kidney function. Heparin is contraindicated for suspected cases of vaccine-induced pro-thrombotic immune thrombocytopenia (VIPIT) secondary to SARS-CoV-2 vaccination, as heparin may further increase the risk of bleeding in an anti-PF4/heparin complex autoimmune manner, in favor of alternative anticoagulant medications (such as arg ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Wnt Signaling Pathway
The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans. Three Wnt signaling pathways have been characterized: the canonical Wnt pathway, the noncanonical planar cell polarity pathway, and the noncanonical Wnt/calcium pathway. All three pathways are activated by the binding of a Wnt-protein ligand to a Frizzled family receptor, which passes the biological signal to the Dishevelled protein inside the cell. The canonical Wnt pathway leads to regulation of gene transcription, and is thought to be negatively regulated in part by the SPATS1 gene. The noncanonical plana ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Agrin
Agrin is a large proteoglycan whose best-characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. In humans, this protein is encoded by the ''AGRN'' gene. This protein has nine domains homologous to protease inhibitors. It may also have functions in other tissues and during other stages of development. It is a major proteoglycan component in the glomerular basement membrane and may play a role in the renal filtration and cell-matrix interactions. Agrin functions by activating the MuSK protein (for Muscle-Specific Kinase), which is a receptor tyrosine kinase required for the formation and maintenance of the neuromuscular junction. Agrin is required to activate MuSK, which is similarly also required for neuromuscular junction formation. Discovery Agrin was first identified by the U.J. McMahan laboratory, Stanford University. Mechani ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fractone
In biology, fractones are structures consisting primarily of laminin and heparan sulfate proteoglycan (HSPG) first discovered in the extracellular matrix niche of the subventricular zone of the lateral ventricle (SVZa) in the mouse brain. Recent research has suggested its importance in adult neurogenesis, gliogenesis, and angiogenesis. Fractones are found near or connected to stem cells, and are highly implicated in cell proliferation, differentiation and migration. New work suggests that fractones are implicated in corticalization during embryogenesis, as well as in cancer and neurodegenerative disease. History The term ''fractone'' is derived from fractal, a term coined by Benoît Mandelbrot in 1975. Fractones were discovered in 2002 in the extracellular matrix niche of the subventricular zone of the lateral ventricule (SVZa) in a mouse brain. Originally found in the neurogenic areas of the brain, recent studies indicate that fractones are also present in multiple organi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Basement Membrane
The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between Epithelium, epithelial tissues including mesothelium and endothelium, and the underlying connective tissue. Structure As seen with the electron microscope, the basement membrane is composed of two layers, the basal lamina and the reticular lamina. The underlying connective tissue attaches to the basal lamina with collagen VII anchoring fibrils and fibrillin microfibrils. The basal lamina layer can further be subdivided into two layers based on their visual appearance in electron microscopy. The lighter-colored layer closer to the epithelium is called the lamina lucida, while the denser-colored layer closer to the connective tissue is called the lamina densa. The Electron microscope, electron-dense lamina densa layer is about 30–70 nanometers thick and consists of an underlying ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glycosaminoglycan
Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case of the sulfated glycosaminoglycan keratan, where, in place of the uronic sugar there is a galactose unit. GAGs are found in vertebrates, invertebrates and bacteria. Because GAGs are highly polar molecules and attract water; the body uses them as lubricants or shock absorbers. Mucopolysaccharidoses are a group of metabolic disorders in which abnormal accumulations of glycosaminoglycans occur due to enzyme deficiencies. Production Glycosaminoglycans vary greatly in molecular mass, disaccharide structure, and sulfation. This is because GAG synthesis is not template driven, as are proteins or nucleic acids, but constantly altered by processing enzymes. GAGs are classified into four groups, based on their core disaccharide structures. Hepa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Iduronic Acid
-Iduronic acid (IUPAC abbr.: IdoA) is the major uronic acid component of the glycosaminoglycans (GAGs) dermatan sulfate, and heparin. It is also present in heparan sulfate, although here in a minor amount relative to its carbon-5 epimer glucuronic acid. IdoA is a hexapyranose sugar. Most hexapyranoses are stable in one of two chair conformations 1C4 or 4C1. -iduronate is different and adopts more than one solution conformation, with an equilibrium existing between three low-energy conformers. These are the 1C4 and 4C1 chair forms and an additional 2S0 skew-boat conformation. IdoA may be modified by the addition of an ''O''-sulfate group at carbon position 2 to form 2-''O''-sulfo--iduronic acid (IdoA2S). In 2000, LK Hallak described the importance of this sugar in respiratory syncytial virus (RSV) infection. Dermatan sulfate and heparan sulfate were the only GAGs containing IdoA, and they were the only ones that inhibited RSV infection in cell culture. When internally position ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Betaglycan
Betaglycan also known as Transforming growth factor beta receptor III (TGFBR3), is a cell-surface chondroitin sulfate / heparan sulfate proteoglycan >300 kDa in molecular weight. Betaglycan binds to various members of the TGF-beta superfamily of ligands via its core protein, and bFGF via its heparan sulfate chains. TGFBR3 is the most widely expressed type of TGF-beta receptor. Its affinity towards all individual isoforms of TGF-beta is similarly high and therefore it plays an important role as a coreceptor mediating the binding of TGF-beta to its other receptors - specifically TGFBR2. The intrinsic kinase activity of this receptor has not yet been described. In regard of TGF-beta signalling it is generally considered a non-signaling receptor or a coreceptor. By binding to various member of the TGF-beta superfamily at the cell surface it acts as a reservoir of TGF-beta. Study of a mouse knock-out for the Tgfbr3 gene showed a fundamental effect on the correct development of organs a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
