CD90
Encyclopedia
style="font-size: larger;" | Thy1/CD90

structure of the protein part of thy1
Claim to fame:
  • Smallest and one of the most conserved members of the immunoglobulin family
  • Lead to the discovery and characterization of GPI anchor
  • Most abundant glycoprotein on mouse T cell
    T cell
    T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

    s, with >106 copies/cell, covering ~10–20% of surface.
  • one of the most heavily glycosylated membrane proteins (carbohydrate content ~30%)
Applications:
  • Very useful specific marker for:
    • Hematopoietic stem cells (FACS
      FACS
      FACS may refer to:* Facial Action Coding System, a procedure to systematically describe human facial expressions.* Fluorescence-activated cell sorting, a biological technique used in flow cytometry.* Family and consumer science...

       gated as Thy1lo)
    • Mesenchymal stem cells
    • Distinction between cells from Thy1.1 and Thy 1.2 mouse strains.
  • Its promoter has been used as a "brain specific" expression promoter for making transgenic mice.
  • Thy1 is a pan T cell antigen in mice.
  • Thy1 antibody injection is the best animal model of glomerulonephritis
    Glomerulonephritis
    Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...

  • Cellular importance:
  • Arrests axon growth
  • Co-stimulator of T cells
  • Regulates survival/apoptosis
  • tumor suppressor
  • fibrosis modulator
  • Organismal importance:
  • knock out of Thy1 shows:
    • impaired cognitive learning from social cues
    • impaired cutaneous immune responses
    • abnormal retinal development
  • :::Thy1's real physiological functions are still not clearly understood

    Thy-1 or CD90 (Cluster of Differentiation 90) is a 25–37 kDa
    Atomic mass unit
    The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...

     heavily N-glycosylated, glycophosphatidylinositol
    Glycophosphatidylinositol
    Glycosylphosphatidylinositol is a glycolipid that can be attached to the C-terminus of a protein during posttranslational modification...

     (GPI) anchored conserved cell surface protein
    Protein
    Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

     with a single V-like immunoglobulin domain
    Immunoglobulin domain
    The immunoglobulin domain is a type of protein domain that consists of a 2-layer sandwich of between 7 and 9 antiparallel β-strands arranged in two β-sheets with a Greek key topology....

    , originally discovered as a thymocyte
    Thymocyte
    Thymocytes are hematopoietic progenitor cells present in the thymus. Thymopoiesis is the process in the thymus by which thymocytes differentiate into mature T lymphocytes. The primary function of thymocytes is the generation of T lymphocytes . The thymus provides an inductive environment, which...

     antigen. Thy-1 can be used as a marker for a variety of stem cell
    Stem cell
    This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...

    s and for the axonal processes
    Axon
    An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....

     of mature neuron
    Neuron
    A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

    s. Structural study of Thy-1 lead to the foundation of the Immunoglobulin superfamily
    Immunoglobulin superfamily
    The immunoglobulin superfamily is a large group of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily based on shared structural features with immunoglobulins ; they all possess a...

    , of which it is the smallest member, and led to the first biochemical description and characterization of a vertebrate GPI anchor.

    Discovery and Nomenclature

    Thy-1 was discovered in early 1960s during the search for heterologous antisera against mouse leukemia
    Leukemia
    Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...

     cells. It was originally named theta (θ) antigen, then Thy-1 (THYmocyte differentiation antigen 1) due to its prior identification in thymocytes (precursors of T cell
    T cell
    T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

    s in the thymus
    Thymus
    The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....

    ). The human homolog was isolated in 1980 as a 25kDa protein (p25) of T-lymphoblastoid cell line MOLT-3 binding with anti-monkey-thymocyte antisera.

    The conserved gene and its alleles

    Thy-1 has been conserved throughout vertebrate evolution and even in some invertebrates, with homologs
    Homology (biology)
    Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...

     described in many species like squid
    Squid
    Squid are cephalopods of the order Teuthida, which comprises around 300 species. Like all other cephalopods, squid have a distinct head, bilateral symmetry, a mantle, and arms. Squid, like cuttlefish, have eight arms arranged in pairs and two, usually longer, tentacles...

    , frog
    Frog
    Frogs are amphibians in the order Anura , formerly referred to as Salientia . Most frogs are characterized by a short body, webbed digits , protruding eyes and the absence of a tail...

    s, chicken
    Chicken
    The chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...

    s, mice
    Mouse
    A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...

    , rat
    Rat
    Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...

    s, dog
    Dog
    The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...

    s, and human
    Human
    Humans are the only living species in the Homo genus...

    s.
    The Thy-1 gene is located at human chromosome
    Chromosome
    A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

     11q22.3 (mouse chromosome 9qA5.1). Some believe that there may be a functional significance of both this gene and CD3 delta subunit (T3D) mapping to chromosome 11q in man and chromosome 9 in mouse, though there is no homology (in fact this speculation lead to its localization in chromosome 11q - the human chromosome region syntenic to mouse chromosome 9 which harbored T3D). In mice, there are two allele
    Allele
    An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...

    s: Thy1.1 (Thy 1a, CD90.1) and Thy1.2 (Thy 1b, CD90.2). They differ by only one amino acid
    Amino acid
    Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

     at position 108; an arginine in Thy-1.1 and a glutamine in Thy-1.2. Thy 1.2 is expressed by most strains of mice, whereas Thy1.1 is expressed by some like AKR/J and PL mouse strains.

    The Protein

    The 25-kDa core protein (excluding the heavy glycosylation) of rodent Thy-1 is 111 or 112 amino acids in length, and is N-glycosylated at three sites (In contrast to only two glycosylation sites for human Thy-1). The 162aa (murine, 161 for human) Thy1 precursor has 19 amino acid (aa 1-19) signal sequence
    Signal sequence
    Signal sequence can refer to:*Protein targeting*Signal peptide*DNA uptake signal sequence...

     and 31 amino acid (aa 132-162) C-terminal transmembrane domain that is present in pro form but removed when transferring the 112 amino acid (aa 20-131) mature peptide to GPI anchor which would attach through the aa 131.

    Some of the common monoclonal antibodies
    Antibody
    An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

     used to detect this protein are clones OX7, 5E10, K117 and L127.
    There have been some reports of Thy1 monoclonal antibodies cross reacting with some cytoskeletal elements: anti Thy-1.2 with actin
    Actin
    Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...

     in marsupial, murine, and human cells and anti Thy-1.1 with vimentin
    Vimentin
    Vimentin is a type III intermediate filament protein that is expressed in mesenchymal cells. IF proteins are found in all metazoan cells as well as bacteria. IF, along with tubulin-based microtubules and actin-based microfilaments, comprise the cytoskeleton...

    , and were suggested to be due to sequence homology by studies done more than 20 years back.

    Thy-1, like many other GPI anchored proteins can be shed by special types of Phospholipase C
    Phospholipase C
    Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. In general, this enzyme is denoted as Phospholipase C, although three other families of phospholipase C enzymes have been identified in bacteria and in...

     e.g. PI-PLC (phosphatidyl-Inositol Phospholipase C, or PLC β). it can also be involved in cell to cell transfer of GPI anchored proteins like CD55 and CD59
    CD59
    Protectin, a complement regulatory protein, also known as ', or MIRL is a human gene and protein....

    .

    Expression

    Thy1 expression varies between species. Amongst the cells reported to generally express Thy-1 areThymocytes (precursor of T cells in the Thymus
    Thymus
    The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....

    ) & CD34
    CD34
    CD34 molecule is a cluster of differentiation molecule present on certain cells within the human body. It is a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of stem cells to bone marrow extracellular matrix or directly to stromal cells...

    (+) prothymocytes; neuron
    Neuron
    A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

    s, mesenchymal stem cells, hematopoietic stem cells, NK cells, murine T-cells, endothelium
    Endothelium
    The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...

    (mainly in High endothelial venules or HEVs where diapedesis takes place), renal glomerular
    Glomerulus
    A glomerulus is a capillary tuft that is involved in the first step of filtering blood to form urine.A glomerulus is surrounded by Bowman's capsule, the beginning component of nephrons in the vertebrate kidney. A glomerulus receives its blood supply from an afferent arteriole of the renal...

     mesangial cell
    Mesangial cell
    Mesangial cells are specialized cells around blood vessels in the kidneys, at the mesangium. They are specialized smooth muscle cells that function to regulate blood flow through the capillaries, usually divided into two types, each having a very distinct function and location:* Extraglomerular...

    s, circulating metastatic melanoma
    Melanoma
    Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...

     cells, Follicular Dendritic Cells (FDC), a fraction of fibroblast
    Fibroblast
    A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...

    s and myofibroblast
    Myofibroblast
    A Myofibroblast is a cell that is in between a fibroblast and a smooth muscle cell in differentiation.-Developmental origin:There are many possible ways of myofibroblast development:#Partial smooth muscle differentiation of a fibroblastic cell...

    s.

    Detailed expression of Thy-1

    • In mice, Thy-1 is also found on thymocytes, peripheral T cells, myoblasts, epidermal cells, and keratinocytes. It is one of the "pan T cell markers"(of mice) like CD2
      CD2
      CD2 is a cell adhesion molecule found on the surface of T cells and natural killer cells.It has also been called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor and rosette receptor....

      , CD5
      CD5
      CD5 or CD-5 may be:* Child development-5, for five-year old children, a more developmentally appropriate acronym for kindergarten* cluster of differentiation 5 molecule, type I transmembrane protein* compact disc, 5-inch CD, usually music CD...

       and CD28
      CD28
      CD28 is one of the molecules expressed on T cells that provide co-stimulatory signals, which are required for T cell activation. CD28 is the receptor for CD80 and CD86 . When activated by Toll-like receptor ligands, the CD80 expression is upregulated in antigen presenting cells...

      .
    • In humans, Thy-1 is also expressed by endothelial cells, smooth muscle cells, a subset of CD34+ bone marrow cells, and umbilical cord blood-, cardiac fibroblasts, and fetal liver-derived hemopoietic cells.

    • Thy-1 is present on a fraction of brain cells and a fraction of fibroblast
      Fibroblast
      A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...

      s of most vertebrate species studied.
    • Nervous tissue: Thy-1 expression in the nervous system is predominantly neuronal, but some glial cells also express Thy-1 especially at later stages of their differentiation. One study compared Thy-1 expression in four human neuronal cell lines, two neuroglial cell lines, and fresh tumor cells of neuronal origin and found three of the four neuronal cell lines, all of the neuroglial cell lines, and 80% of the tumors to be strongly positive for Thy-1. Brain part specific ELISA reports are available which show highest concentrations of Thy1 protein in the striatum
      Striatum
      The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...

       and hippocampus
      Hippocampus
      The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

      , followed by the neocortex
      Neocortex
      The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...

      , cerebellum
      Cerebellum
      The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...

      , spinal cord
      Spinal cord
      The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

      , and the retina
      Retina
      The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...

       and optic nerve
      Optic nerve
      The optic nerve, also called cranial nerve 2, transmits visual information from the retina to the brain. Derived from the embryonic retinal ganglion cell, a diverticulum located in the diencephalon, the optic nerve doesn't regenerate after transection.-Anatomy:The optic nerve is the second of...

      . Thy1 promoter has often been assumed to be "brain specific". "Neuron specific" mouse thy1 promoter has been used to drive "brain specific" forced expression of proteins e.g. mutated Amyloid precursor protein
      Amyloid precursor protein
      Amyloid precursor protein is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation, neural plasticity and iron export...

      (APP) as transgenic animal models of Alzheimer's disease
      Alzheimer's disease
      Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

      . Thy-1 expression in the brain is developmentally regulated. Thy-1 levels in the neonatal rat brain, as well as the developing human brain, are low compared to adult brain. During the first few weeks of postnatal development, Thy-1 levels increase exponentially as the brain matures.
    • Lymphoid tissue Thy-1 expression is highly variable between species. In humans, Thy-1 expression is restricted to only a small population of cortical thymocytes and not expressed in mature human T cells. It is probably the most abundant glycoprotein of murine thymocytes, with about One million copies per cell covering up to 10–20% of the cell surface. Mouse cortical thymocytes express higher levels of Thy-1 than medullary thymocytes which in turn express more than lymph node cells (~200,000 copies/cell). A similar inverse developmental temporal expression profile is seen in rats T cells, although rat Thy-1 is lost at an earlier stage of T cell maturation. Thy-1 is only expressed on thymocytes in rats (contrast to thymocytes and splenocytes in mice). The third intron of the mouse Thy-1 gene has a 36 base pair region that recruits nuclear transcription factors, such as Ets-1-like NF, expressed in thymocytes and splenocytes. The homologous region of the rat gene lacks the Ets-1-like NF binding site, but instead binds another NF expressed in rat thymocytes but not splenocytes.

    Induction of Thy-1 expression

    • Agents shown to induce Thy1 expression include: Thymopoietin
      Thymopoietin
      Lamina-associated polypeptide 2, isoforms beta/gamma is a protein that in humans is encoded by the TMPO gene.Thymopoietin is a protein involved in the induction of CD90 in the thymus. The thymopoetin gene encodes three alternatively spliced mRNAs encoding proteins of 75 kDa , 51 kDa and 39 kDa ...

      , thymosin
      Thymosin
      Thymosins are small proteins present in many animal tissues. They are named thymosins because they were originally isolated from the thymus, but most are now known to be present in many other tissues...

      , prostaglandins, nerve growth factor
      Nerve growth factor
      Nerve growth factor is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons . It also functions as a signaling molecule. It is perhaps the prototypical growth factor, in that it is one of the first to be described...

      , IL-1
      IL-1
      IL-1 may refer to:* Interleukin 1, a protein* Illinois' 1st congressional district* Illinois Route 1* Building 1 of Infinite Loop , the Headquarters of Apple Inc....

      , TNF
      Tumor necrosis factors
      Tumor necrosis factors refers to a group of cytokines family that can cause cell death . The first two members of the family to be identified were:...

      , PMA
      PMA
      para-Methoxyamphetamine , also known as 4-methoxyamphetamine , is a serotonergic drug of the amphetamine class...

      , Ca2+ ionophore, and diacylglycerol
      Diglyceride
      A diglyceride, or a diacylglycerol , is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages....

       (DAG).

    Localization

    As a GPI-anchored protein
    Glycophosphatidylinositol
    Glycosylphosphatidylinositol is a glycolipid that can be attached to the C-terminus of a protein during posttranslational modification...

    , Thy-1 is present in the outer leaflet of lipid raft
    Lipid raft
    The plasma membrane of cells is made of a combination of glycosphingolipids and protein receptors organized in glycolipoprotein microdomains termed lipid rafts...

    s in the cell membrane. In case of neuron
    Neuron
    A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

    s it is known to be expressed strongly in the mature axon. The axon hillock
    Axon hillock
    The axon hillock is a specialized part of the cell body of a neuron that connects to the axon. As a result, the axon hillock is the last site in the soma where membrane potentials propagated from synaptic inputs are summated before being transmitted to the axon. For many years it was believed...

     can act as a barrier for its lateral spread even though it has no transmembrane segment. Thy-1 has been suggested to interact with G inhibitory proteins, the Src family kinase (SFK) member c-fyn, and tubulin within lipid rafts. In rats and mice, Thy-1 protein is present on the soma (cell body) and dendrites of neurons but is not expressed on axons until axonal growth is complete, and is again temporarily suppressed during axonal injury. HIV-1 Matrix co-localizes with Thy-1 in lipid rafts, the site of virus particle budding from cells, and Thy-1 is incorporated into virus particles as a result of this process.

    Glycosylation

    Thy-1 is one of the most heavily glycosylated membrane proteins with a carbohydrate content up to 30% of its molecular mass. The composition of Thy-1 carbohydrate moieties varies considerably between different tissues or even among cells of the same lineage at different stages of differentiation: e.g., galactosamine only in brain Thy-1, sialic acid in thymic Thy-1 in far excess than brain Thy-1, that too increasing in parallel with T cell maturation

    Function

    The function of Thy-1 has not yet been fully elucidated. It has speculated roles in cell-cell and cell-matrix interactions, with implication in neurite outgrowth, nerve regeneration, apoptosis
    Apoptosis
    Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

    , metastasis
    Metastasis
    Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

    , inflammation
    Inflammation
    Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

    , and fibrosis
    Fibrosis
    Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...

    .

    Role in cognition

    The Thy-1 knockout (KO) mice are viable and appear grossly normal. They display normal social interactions and normal learning in a maze, but fail to learn from social cues (e.g. learning from other mice which foods are safe to eat as compared to wild-type mice). This failure can be rescued by the transgenic expression of Thy-1 or pharmacologic treatment with a GABA (A) receptor antagonists. This suggests that Thy-1 KO mice have excessive GABAergic inhibition in the dentate gyrus and regional inhibition of long-term potentiation.

    Axon growth regulation

    Crosslinking anti-Thy-1 Ab can promote neurite outgrowth which is dependent on G{alpha}i and L- and N-type calcium channel activation. The ligand for promotion of neurite outgrowth on astrocytes is not yet identified, but the inhibitory ligand has been suggested to be integrins. Thy1 is one of the known ligands of beta 3 integrin
    Integrin
    Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....

    s. Interaction of thy1 expressed on maturing axon
    Axon
    An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....

    s with beta 3 integrins expressed on mature astrocytes may be the cause of halting of axon growth.

    T-cell activation

    Crosslinking Thy-1 molecules in the membrane raft, in the context of strong costimulatory signaling through CD28 in mouse T cells can act to some extent as a substitute activating signal for T-cell receptor signaling. Conversely it can substitute CD28 costimulation for activation through the TCR.

    Apoptosis/Necrosis

    Cross linking antibody induced aggregation of Thy1 cause death of thymocytes and mesangial cells mainly by apoptosis
    Apoptosis
    Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

     despite Bcl2 upregulation. The death of mesangial cells seems to be apoptosis by TUNEL staining or annexin V staining, but electron microscopy suggest it is necrosis
    Necrosis
    Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...

    .

    Antibody target for animal model of Glomerulonephritis

    Single tail vein intravenous injection of antibody (OX7 mouse monoclonal
    Monoclonal
    Monoclonal cells are defined as a group of cells produced from a single ancestral cell by repeated cellular replication. Thus they can be said to form a single "clone". The process of replication can occur in vivo, or may be stimulated in vitro for laboratory manipulations...

     IgG) against Thy1.1 in rats is used as a standard animal model to produce experimental mesangioproliferative glomerulonephritis
    Glomerulonephritis
    Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...

     which is popularly known in the field of nephrology
    Nephrology
    Nephrology is a branch of internal medicine and pediatrics dealing with the study of the function and diseases of the kidney.-Scope of the specialty:...

     as antiThy1 GN.

    Tumor suppression

    It has also been proven to be a tumor suppressor for some tumors. It probably is aided by its action in upregulating thrombospondin
    Thrombospondin
    Thrombospondins are secreted proteins with antiangiogenic abilities. TSP was discovered by Nancy L. Baenziger.-Types:The thrombospondins are a family of multifunctional proteins...

    , SPARC
    SPARC
    SPARC is a RISC instruction set architecture developed by Sun Microsystems and introduced in mid-1987....

     (osteonectin
    Osteonectin
    Osteonectin also known as secreted protein acidic and rich in cysteine or basement-membrane protein 40 is a protein that in humans is encoded by the SPARC gene....

    ), and fibronectin
    Fibronectin
    Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...

    . However it has also been speculated to aid in extravasation in circulating melanoma cells. In case of prostate cancer it has been shown to be expressed in cancer associated stroma but not in normal stroma and has been suggested to be of potential help for cancer specific drug targeting http://www3.niddk.nih.gov/fund/other/cellularniche/poster%20abstracts/True%20Abstract%20ormatted.pdf.

    Role in cell adhesion, extravasation, migration

    Acting through several integrins and probably a few yet unknown other receptors Thy-1 mediates adhesion of leukocytes and monocytes to endothelial cells and fibroblasts, melanoma cells to endothelium, and thymocytes to thymic epithelium. Thy1 expression comes on when endothelial cells are activated. It has been shown to interact with the leukocyte integrin Mac1 (CD11b/CD18) and may play a role in leukocyte homing and recruitment.

    Modulating fibrosis

    Role of Thy-1 in fibrosis and fibroblast differention may have some tissue variation. In lung fibrosis Thy-1 level is suppressed in stimulated fibroblasts. Thy1 knock out mice have increased fibrosis in the lung. Fibrosis induced by radiation mimicking chemotherapeutic agent Bleomycin
    Bleomycin
    Bleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA...

     is also increased in these mice.

    Other roles

    Thy-1 knock out mice also show impaired cutaneous immune responses and abnormal retinal development: thinning of the inner nuclear, inner plexiform, ganglion cell, and outer segment layers of the retina.

    Use in stem cell biology

    Thy-1 can be considered as a surrogate marker for various kind of stem cell
    Stem cell
    This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...

    s (e.g. hematopoietic stem cells or HSCs). It is one of the popular combinatorial surface markers for FACS for stem cells in combination with other markers like CD34
    CD34
    CD34 molecule is a cluster of differentiation molecule present on certain cells within the human body. It is a cell surface glycoprotein and functions as a cell-cell adhesion factor. It may also mediate the attachment of stem cells to bone marrow extracellular matrix or directly to stromal cells...

    . During sorting, mouse HSCs fall under Thy1hi subpopulation, while human HSCs fall under the Thy1lo subpopulation. In humans, Thy-1 is expressed on neurons and HSCs among others. It is considered a major marker of HSC pluripotency in concordance with CD34. In human HSCs, Thy1 cells are all CD34 positive.Thy 1 is also a marker of other kind of stem cells, for example: mesenchymal stem cells, hepatic stem cells ("oval cells"), keratinocyte stem cells, putative endometrial progenitor/(?)stem cells.
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