Macrophage inducible Ca²⁺-dependent lectin receptor, (abbreviated to Mincle), is a member of the

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 ...

superfamily encoded by the gene CLEC4E. It is a

pattern recognition receptor Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed, mainly, by cells of ...

that can recognize glycolipids including mycobacterial

cord factor Cord factor, or trehalose dimycolate, is a glycolipid molecule found in the cell wall of '' Mycobacterium tuberculosis'' and similar species. It is the primary lipid found on the exterior of ''M. tuberculosis'' cells. Cord factor influences the ...

, trehalose-6,6'-dimycolate (TDM). The mincle receptor binds a range of carbohydrate structures, predominantly containing glucose or mannose, and play an important role in recognition of bacterial glycolipids by the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

. Upon activation by cord factor, Mincle binds the Fc receptor FcRγ and

Syk Tyrosine-protein kinase SYK, also known as spleen tyrosine kinase, is an enzyme which in humans is encoded by the ''SYK'' gene. Function SYK, along with ZAP70, is a member of the Syk family of tyrosine kinases. These cytoplasmic non-receptor t ...

. Cord factor also binds and activates the related C-type lectin MCL. Upon receptor stimulation is PKC-δ activated, which subsequently phosphorylates

CARD9 Caspase recruitment domain-containing protein 9 is an adaptor protein of the CARD-CC protein family, which in humans is encoded by the ''CARD9'' gene. It mediates signals from pattern recognition receptors to activate pro-inflammatory and anti-i ...

that triggers recruitment of

BCL10 B-cell lymphoma/leukemia 10 is a protein that in humans is encoded by the ''BCL10'' gene. Like BCL2, BCL3, BCL5, BCL6, BCL7A, and BCL9, it has clinical significance in lymphoma. Function Bcl10 was identified by its translocation in a case of ...

and

MALT1 Mucosa-associated lymphoid tissue lymphoma translocation protein 1 is a protein that in humans is encoded by the ''MALT1'' gene. It's the human paracaspase. Function Genetic ablation of the paracaspase gene in mice and biochemical studies have ...

, leading to a CARD-CC/

(CBM) signaling complex. This signaling complex in turn triggers downstream recruitment of

TRAF6 TRAF6 is a TRAF human protein. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF recep ...

and

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...

activation. A wide range of ligands promote signalling through Mincle, including proteins, sterols and glycolipids from altered or damaged self, and various glycolipids from pathogenic and commensal organisms.

Mincle agonists from self

Crystalline cholesterol, which accumulates in atherosclerotic lesions, can signal through human Mincle. Cholesterol sulfate, which is present in the skin, is a cause of sterile inflammation through agonizing Mincle signalling. The protein SAP130 signal through Mincle. Beta-glucosylceramide, which accumulates as a result of the lysosomal storage disorder Gaucher’s disease, signals through Mincle.

Mincle agonists from microbes

Mycobacteria and corynebacteria produce a wide range of glycolipids that can signal through Mincle. These include glucose and trehalose mycolates, and their closely related corynomycolates from mycobacteria and corynebacteria. Glycosyl diglycerides from various pathogenic and commensal bacteria and fungi such as ''Lactobacillus plantarum'', ''Streptococcus pneumoniae'', ''Mycobacterium tuberculosis'' and ''Malassezia'' sp.

References

{{Transmembranereceptor-stub

Mincle agonists from self

Mincle agonists from microbes

See also

References