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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''CLEC10A''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
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
oocyte
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 ger ...
s and very early stages of
embryogenesis
An embryo ( ) is the initial stage of development for 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 ...
. CLEC10A is used as a marker of the
CD1c+ dendritic cell
A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's 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_junction, cell junc ...
,
cell-cell signalling,
glycoprotein
Glycoproteins are proteins which contain oligosaccharide (sugar) 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 a ...
turnover, and roles in
inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
and immune response.
CLEC10A is a
type II transmembrane protein (passing one time through the membrane and oriented with the
N terminus
N, or n, is the fourteenth letter of the Latin alphabet, used in the modern English alphabet, the alphabets of other western European languages, and others worldwide. Its name in English is ''en'' (pronounced ), plural ''ens''.
History
...
inward) that induces
endocytosis
Endocytosis is a cellular process in which Chemical substance, 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 (biology and chem ...
after
ligand
In coordination chemistry, a ligand is an ion or molecule with a 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 el ...
binding. To release the ligand in the
endosome
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of the endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membra ...
, 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 (, ''wikt:galacto-, galacto-'' + ''wikt:-ose#Suffix 2, -ose'', ), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweetness, sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epime ...
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
carcinoma
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 ...
s, 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
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 monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
s 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 sequence ...
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 and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...
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
T cells (also known as T lymphocytes) are an important part 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 receptor (TCR) on their cell ...
activity,
apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
, 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 react ...
. 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 Ca
2+ result in production of
IL-12, a pro-inflammatory 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 inflammation.
References
Further reading
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External links
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{{Lectins
C-type lectins