CD93 (Cluster of Differentiation 93) is a
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 ...
that in humans is encoded by the ''CD93''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
CD93 is a
C-type lectin
A C-type lectin (CLEC) is a type of carbohydrate-binding protein known as a lectin. The C-type designation is from their requirement for calcium for binding. Proteins that contain C-type lectin domains have a diverse range of functions including ...
transmembrane receptor which plays a role not only in cell–cell adhesion processes but also in host defense.
Family
CD93 belongs to the Group XIV C-Type
lectin
Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in rec ...
family, a group containing three other members, endosialin (
CD248
Endosialin is a protein that in humans is encoded by the ''CD248'' gene.
Endosialin is a member of the “ Group XIV”, a novel family of C-type lectin transmembrane receptors which play a role not only in cell–cell adhesion processes but also ...
), CLEC14A and
thrombomodulin
Thrombomodulin (TM), CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells and serves as a cofactor for thrombin. It reduces blood coagulation by converting thrombin to an anticoagulant enzyme from a procoa ...
, a well characterized anticoagulant. All of them contain a C-type lectin domain, a series of
epidermal growth factor like domains, a highly glycosylated mucin-like domain, a unique transmembrane domain and a short cytoplasmic tail. Due to their strong homology and their close proximity on chromosome 20, CD93 has been suggested to have arisen from the thrombomodulin gene through a
duplication
Duplication, duplicate, and duplicator may refer to:
Biology and genetics
* Gene duplication, a process which can result in free mutation
* Chromosomal duplication, which can cause Bloom and Rett syndrome
* Polyploidy, a phenomenon also known ...
event.
Expression
CD93 was originally identified in mice as an early
B cell
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
marker through the use of AA4.1 monoclonal antibody.
Then this molecule was shown to be expressed on an early population of
hematopoietic stem cell
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 ...
s, which give rise to the entire spectrum of mature cells in the blood. Now CD93 is known to be expressed by a wide variety of cells such as
platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
s,
monocyte
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...
s,
microglia
Microglia are a type of neuroglia (glial cell) located throughout the brain and spinal cord. Microglia account for about 7% of cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune de ...
and
endothelial
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 ...
cells. In the immune system CD93 is also expressed on
neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
s, activated
macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s, B cell precursors until the T2 stage in the spleen, a subset of dendritic cells and of natural killer cells. Molecular characterization of CD93 revealed that this protein is identical with C1qRp, a human protein identified as a putative
C1q
The complement component 1q (or simply C1q) is a protein complex involved in the complement system, which is part of the innate immune system. C1q together with C1r and C1s form the C1 complex.
Antibodies of the adaptive immune system can bi ...
receptor.
C1q belongs to the
complement
A complement is something that completes something else.
Complement may refer specifically to:
The arts
* Complement (music), an interval that, when added to another, spans an octave
** Aggregate complementation, the separation of pitch-class ...
activation proteins and plays a major role in the activation of the classical pathway of the complement, which leads to the formation of the membrane attack complex. C1q is also involved in other immunological processes such as enhancement of bacterial phagocytosis, clearance of
apoptotic
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 includ ...
cells or neutralisation of virus. Strikingly, it has been shown that anti-C1qRp significantly reduced C1q enhanced phagocytosis. A more recent study confirmed that C1qRp is identical to CD93 protein, but failed to demonstrate a direct interaction between CD93 and C1q under physiological conditions. Recently it has been shown that CD93 is re-expressed during the late B cell differentiation and CD93 can be used in this context as a plasma cell maturation marker. CD93 has been found to be differentially expressed in grade IV glioma vasculature when compared to low grade glioma or normal brain and its high expression correlated with the poor survival of the patients.
Function
CD93 was initially thought to be a receptor for C1q, but now is thought to instead be involved in intercellular
adhesion
Adhesion is the tendency of dissimilar particles or surfaces to cling to one another ( cohesion refers to the tendency of similar or identical particles/surfaces to cling to one another).
The forces that cause adhesion and cohesion can be ...
and in the clearance of apoptotic cells. The intracellular cytoplasmic tail of this protein contains two highly conserved domains which may be involved in CD93 function. Indeed, the highly charged juxtamembrane domain has been found to interact with
moesin
Moesin is a protein that in humans is encoded by the ''MSN'' gene.
Moesin (for membrane-organizing extension spike protein) is a member of the ERM protein family which includes ezrin and radixin. ERM proteins appear to function as cross-linkers b ...
, a protein known to play a role in linking transmembrane proteins to the
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
and in the remodelling of the cytoskeleton. This process appears crucial for both adhesion,
migration
Migration, migratory, or migrate may refer to: Human migration
* Human migration, physical movement by humans from one region to another
** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...
and
phagocytosis
Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...
, three functions in which CD93 may be involved.
In the context of late B cell differentiation, CD93 has been shown to be important for the maintenance of high antibody titres after immunization and in the survival of long-lived plasma cells in the bone marrow. Indeed, CD93 deficient mice failed to maintain high antibody level upon immunization and present a lower amount of antigen specific plasma cells in the bone marrow.
In the context of the endothelial cells, CD93 is involved in endothelial cell-cell adhesion, cell spreading, cell migration, cell polarization as well as tubular morphogenesis.
Recently it has been found that CD93 is able to control endothelial cell dynamics through its interaction with an extracellular matrix gycoprotein MMRN2.
Absence of CD93 or its interacting partner MMRN2 in the endothelial cells lead to disruption of extracellular matrix protein
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 ...
fibrillogenesis and decreased
integrin B1 activation.
CD93 plays a significant role in the glioma development. CD93 knockout mice with glioma show smaller tumor size and improved survival.
The tumors also show disrupted fibronectin fibrillogenesis and decreased
integrin B1 activation.
See also
*
Cluster of differentiation
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophen ...
*
C-type lectin
A C-type lectin (CLEC) is a type of carbohydrate-binding protein known as a lectin. The C-type designation is from their requirement for calcium for binding. Proteins that contain C-type lectin domains have a diverse range of functions including ...
References
Further reading
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External links
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{{Clusters of differentiation
Clusters of differentiation