C-type lectin domain family 10 member A (CLEC10A) also designated as CD301 is a protein that in humans is encoded by the ''CLEC10A'' gene. 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 and very early stages of

embryogenesis An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...

. CLEC10A is used as a marker of the CD1c⁺

dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...

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 adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...

, cell-cell signalling,

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

turnover, and roles in inflammation and immune response. CLEC10A is a type II transmembrane protein (passing one time through the membrane and oriented with the N terminus inward) that induces

endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...

after ligand binding. To release the ligand in the endosome, 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 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, 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 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 infl ...

recruited to inflammatory environments. CD45 contains a Tn antigen in

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

B. CD45 has 3 important exons (4,5,6), that are designated A,B,C. Isoforms 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 activity,

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 ...

, and immunosuppression. 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