C-type lectin domain family 10 member A (CLEC10A) also designated as CD301 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, res ...

that in humans is encoded by the ''CLEC10A''

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 b ...

. CLEC10A is part of the C-type lectin superfamily and binds to ''N''-Acetylgalactosamine (GalNAc). It is mainly expressed on

myeloid cells A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow (can be found in circulating blood when caused by certain diseases). Structure When stained with the usual dyes, the cytoplasm is distinctly basophilic ...

and also on

oocytes An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female g ...

and very early stages of embryogenesis. CLEC10A is used as a marker of the CD1c⁺ dendritic cell subgroup, also called cDC2. The actions of CLEC10A are diverse, depending on the ligand and environment.

Function

Generally, C-type lectins bind carbohydrate moieties usually in the presence of Ca2⁺ and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

and immune response. CLEC10A is a type II transmembrane protein (passing one time through the membrane and oriented with the

N terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

inward) that induces endocytosis after

ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...

binding. To release the ligand in the

endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...

, participating Ca2⁺ ions have to be unbound first. This leads to a significant increase in cytoplasmic Ca2⁺ concentration. CLEC10A binds most strongly to ''N''-Acetylgalactosamine (GalNAc), preferring α-GalNAc over β-GalNAc, unmodified

galactose Galactose (, '' galacto-'' + ''-ose'', "milk sugar"), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epimer of glucose. A galactose molecu ...

is bound very weakly. CLEC10A is the only C-type lectin within the human immune system that exclusively recognizes terminal GalNAc. This includes the Tn antigen (GalNAc O-bound to serine or threonine) which is prominently expressed on

carcinomas Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoder ...

, where it can also be sialylated. These tumor-associated antigens (Neu5Acα2,6-Tn, and NeuGcα2,6-Tn) are also bound. CLEC10A has also been shown to bind GalNAc in the teichoic acid of the Staphylococcus aureus cell wall and the surface of parasites. CLEC10A is expressed by dendritic cells that differentiate from monocytes recruited to inflammatory environments.

CD45 Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the ''PTPRC'' gene. PTPRC is also known as CD45 antigen (CD stands for cluster of differentiation), which was originally called leuko ...

contains a Tn antigen in exon B. CD45 has 3 important exons (4,5,6), that are designated A,B,C.

Isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some iso ...

of CD45 are labeled depending on the presence of these exons. CLEC10A can for example bind CD45RB or CD45R, which is shorthand for CD45RABC. Binding causes attenuation 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 ...

activity, apoptosis, and

immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...

. However, active T cells express shorter isoforms of CD45 (CD45RO, CD45RA) that lack exon B. CLEC10A signalling induces IL-10 production in dendritic cells, in part through increasing intracellular Ca2⁺ concentration. IL-10 is the main regulatory and anti-inflammatory cytokine produced in humans. In contrast, low concentrations of intracellular Ca²⁺ result in production of IL-12, a pro-inflamatory cytokine that also leads to Th1 polarisation. In cancer research, CLEC10A expression was found to both improve and worsen survival. In animal models, deficiency of the orthologue to CLEC10A, Mgl1 is associated with worse outcomes in infection and excessive inflamation.

Function

References

External links

Further reading