Thy-1 or CD90 (Cluster of Differentiation 90) is a 25–37 k Da heavily N-glycosylated,

glycophosphatidylinositol Glycosylphosphatidylinositol (), or glycophosphatidylinositol, or GPI in short, is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in ...

(GPI) anchored conserved cell surface

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

with a single V-like

immunoglobulin domain The immunoglobulin domain, also known as the immunoglobulin fold, is a type of protein domain that consists of a 2-layer sandwich of 7-9 antiparallel β-strands arranged in two β-sheets with a Greek key topology, consisting of about 125 amino ac ...

, originally discovered as a

thymocyte A Thymocyte is an immune cell present in the thymus, before it undergoes transformation into a T cell. Thymocytes are produced as stem cells in the bone marrow and reach the thymus via the blood. Thymopoiesis describes the process which turns thymo ...

antigen. Thy-1 can be used as a marker for a variety of

stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...

s and for the axonal processes of mature

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

s. Structural study of Thy-1 led to the foundation of the

Immunoglobulin superfamily The immunoglobulin superfamily (IgSF) is a large protein superfamily 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 ba ...

, of which it is the smallest member, and led to some of the initial biochemical description and characterization of a vertebrate GPI anchor and also the first demonstration of tissue specific differential glycosylation.

Discovery and nomenclature

The antigen Thy-1 was the first T cell marker to be identified. Thy-1 was discovered by Reif and Allen in 1964 during a search for heterologous antisera against mouse

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

cells, and was demonstrated by them to be present on murine thymocytes, on T lymphocytes, and on neuronal 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 A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

s in the

thymus The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...

). 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 discovery of Thy-1 in mice and humans led to the subsequent discovery of many other T cell markers, which is very significant to the field of

immunology Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see there ...

since T cells (along with B cells) are the major cellular components of the adaptive immune response.

The conserved gene and its alleles

Thy-1 has been conserved throughout vertebrate evolution and even in some invertebrates, with

homologs A couple of homologous chromosomes, or homologs, are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during fertilization. Homologs have the same genes in the same locus (genetics), loci where they pr ...

described in many species like

squid True squid are molluscs with an elongated soft body, large eyes, eight arms, and two tentacles in the superorder Decapodiformes, though many other molluscs within the broader Neocoleoidea are also called squid despite not strictly fitting t ...

frog A frog is any member of a diverse and largely Carnivore, carnivorous group of short-bodied, tailless amphibians composing the order (biology), order Anura (ανοὐρά, literally ''without tail'' in Ancient Greek). The oldest fossil "proto-f ...

chicken The chicken (''Gallus gallus domesticus'') is a domesticated junglefowl species, with attributes of wild species such as the grey and the Ceylon junglefowl that are originally from Southeastern Asia. Rooster or cock is a term for an adult m ...

mice A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

, rats,

dog The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. Do ...

s, and

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

s. The Thy-1 gene is located at human

chromosome 11 Chromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 135 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...

q22.3 (mouse chromosome 9qA5.1). I
AceView
it covers 6.82 kb, from 119294854 to 119288036 (NCBI 37, August 2010), on the reverse strand. This locus is very close to CD3 & CD56/

NCAM Neural cell adhesion molecule (NCAM), also called CD56, is a homophilic binding glycoprotein expressed on the surface of neurons, glia and skeletal muscle. Although CD56 is often considered a marker of neural lineage commitment due to its discover ...

genes. 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 led to its localization in chromosome 11q - the human chromosome region syntenic to mouse chromosome 9 which harbored T3D). In mice, there are two

allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

s: Thy1.1 (Thy 1a, CD90.1) and Thy1.2 (Thy 1b, CD90.2). They differ by only one

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

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 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 An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

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 is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...

in marsupial, murine, and human cells and anti Thy-1.1 with

vimentin Vimentin is a structural protein that in humans is encoded by the ''VIM'' gene. Its name comes from the Latin ''vimentum'' which refers to an array of flexible rods. Vimentin is a type III intermediate filament (IF) protein that is expressed ...

, 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 (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role ...

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 Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the ''CD55'' gene. DAF regulates the complement system on the cell surface. It recognizes C4b and C3b fragments that are created during a ...

and

CD59 CD59 glycoprotein, also known as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin, is a protein that in humans is encoded by the ''CD59'' gene. It is an LU domain and belongs to the LY6/uPAR/ alpha-ne ...

Glycosylation

Thy-1 is one of the most heavily glycosylated membrane proteins with a carbohydrate content up to 30% of its molecular mass. Thy1 in most species has 3 N-glycosylation sites (Asn 23, 74 and 98) but no O-glycosylation. 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. In this regard it has yet another historic association: Thy1 happens to be the first glycoprotein in which cell type specificity of variant glycosylation on an invariant protein was demonstrated. Analysis of Differencial glycosylation of Thy-1 from brain and thymus showed that all the complex N-linked structures differed between the two forms, superimposed upon a site specific common core. In case of Thy1 this core pattern was constituted by Asn23 carrying mostly oligomannose structures, Asn74 carrying the most extended complex structures, and Asn98 carrying smaller complex structure. The structure of the sugar residues in the GPI anchor and their associated esterified structures (e.g. additional fatty acids and alcohols) also can be cell type and species specific.

Expression

Thy1 expression varies between species. Amongst the cells reported to generally express Thy-1 are

thymocytes A Thymocyte is an immune cell present in the thymus, before it undergoes transformation into a T cell. Thymocytes are produced as stem cells in the bone marrow and reach the thymus via the blood. Thymopoiesis describes the process which turns thymo ...

(precursor of T cells in the

) &

CD34 CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first descri ...

(+) prothymocytes;

mesenchymal stem cells Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage ce ...

hematopoietic stem cells Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within t ...

NK cell Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represen ...

s, murine

T-cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...

endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

(mainly in

high endothelial venule High endothelial venules (HEV) are specialized post-capillary venous swellings characterized by plump endothelial cells as opposed to the usual thinner endothelial cells found in regular venules. HEVs enable lymphocytes circulating in the blood t ...

s or HEVs where diapedesis takes place), renal

glomerular ''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to: * the filte ...

mesangial cell Mesangial cells are specialised cells in the kidney that make up the mesangium of the glomerulus. Together with the mesangial matrix, they form the vascular pole of the renal corpuscle. The mesangial cell population accounts for approximately 30 ...

s, circulating metastatic

melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

cells,

follicular dendritic cell Follicular dendritic cells (FDC) are cells of the immune system found in primary and secondary lymph follicles (lymph nodes) of the B cell areas of the lymphoid tissue. Unlike dendritic cells (DC), FDCs are not derived from the bone-marrow hema ...

s (FDC), a fraction of

fibroblast A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...

s and

myofibroblast A myofibroblast is a cell phenotype that was first described as being in a state between a fibroblast and a smooth muscle cell. Structure Myofibroblasts are contractile web-like fusiform cells that are identifiable by their expression of α-sm ...

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 (cluster of differentiation 2) is a cell adhesion molecule found on the surface of T cells and natural killer (NK) cells. It has also been called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor and rosette rece ...

, CD5 and

CD28 CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival. T cell stimulation through CD28 in addition to the T-cell receptor ( TCR) can provid ...

. * 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

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 The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamate ...

and

hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...

, followed by the

neocortex The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, sp ...

cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...

, and the

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...

and

optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual system, visual information from the retina to the brain. In humans, the optic nerve i ...

. 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-beta precursor protein (APP) is an integral membrane protein expressed in many biological tissue, tissues and concentrated in the synapses of neurons. It functions as a cell surface receptor and has been implicated as a regulator ...

(APP) as transgenic animal models of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

. 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 Lamina-associated polypeptide 2 (LAP2), isoforms beta/gamma is a protein that in humans is encoded by the ''TMPO'' gene. LAP2 is an inner nuclear membrane (INM) protein. Thymopoietin is a protein involved in the induction of CD90 in the thymus. ...

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. Thymosins have diverse biological activities, ...

prostaglandins The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...

nerve growth factor Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was on ...

, IL-1,

TNF Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

, PMA, Ca2+ ionophore, and

diacylglycerol A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. DAGs can act as sur ...

(DAG).

Localization

As a

GPI-anchored protein Lipid-anchored proteins (also known as lipid-linked proteins) are proteins located on the surface of the cell membrane that are covalently attached to lipids embedded within the cell membrane. These proteins insert and assume a place in the bilay ...

, Thy-1 is present in the outer leaflet of

lipid raft The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains somewhat controversial. ...

s in the cell membrane. In case of

s it is known to be expressed strongly in the mature axon. The

axon hillock The axon hillock is a specialized part of the cell body (or soma) of a neuron that connects to the axon. It can be identified using light microscopy from its appearance and location in a neuron and from its sparse distribution of Nissl substance. ...

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 The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey, ...

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.

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 (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

, and

fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

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 Gi 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 Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...

s. Interaction of thy1 expressed on maturing

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action po ...

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.

Cell death

Cross linking antibody induced aggregation of Thy1 cause death of thymocytes and mesangial cells mainly by

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 () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

Antibody target for animal model of glomerulonephritis

Single tail vein intravenous injection of antibody (OX7 mouse

monoclonal Monoclonality refers to the state of a line of cells that have been derived from a single clonal origin. Thus "monoclonal cells" can be said to form a single clone. The term ''monoclonal'' comes from the Ancient Greek ''monos'', meaning "alone" o ...

IgG) against Thy1.1 in rats is used as a standard animal model to produce experimental mesangioproliferative

glomerulonephritis Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the ...

which is popularly known in the field of

nephrology Nephrology (from Greek'' nephros'' "kidney", combined with the suffix ''-logy'', "the study of") is a specialty of adult internal medicine and pediatric medicine that concerns the study of the kidneys, specifically normal kidney function (ren ...

as ''antiThy1 GN''.

Tumor suppression

It has also been proven to be a

tumor suppressor A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or red ...

for some tumors. It probably is aided by its action in upregulating

thrombospondin Thrombospondins (TSPs) are a family of secreted glycoproteins with antiangiogenic functions. Due to their dynamic role within the extracellular matrix they are considered matricellular proteins. The first member of the family, thrombospondin 1 (T ...

, SPARC (

osteonectin Osteonectin (ON) also known as secreted protein acidic and rich in cysteine (SPARC) or basement-membrane protein 40 (BM-40) is a protein that in humans is encoded by the ''SPARC'' gene. Osteonectin is a glycoprotein in the bone that binds calciu ...

), and

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...

. 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 targetin

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. Thy1 knock out mice have increased fibrosis in the lung. Fibrosis induced by chemotherapeutic agent

Bleomycin -13- (1''H''-imidazol-5-yl)methyl9-hydroxy-5- 1''R'')-1-hydroxyethyl8,10-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazapentadec-1-yl}-2,4'-bi-1,3-thiazol-4-yl)carbonyl]amino}propyl)(dimethyl)sulfonium , chemical_formula = , C=55 , H=84 , N=1 ...

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

s (e.g.

or HSCs). It is one of the popular combinatorial surface markers for Fluorescent-activated cell sorting, FACS for stem cells in combination with other markers like

. 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 The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

("oval cells"), keratinocyte stem cells, putative endometrial progenitor/(?)stem cells.

References

External links

* {{Clusters of differentiation Molecular biology Clusters of differentiation