Mincle receptor explained

Macrophage inducible Ca2+-dependent lectin receptor, (abbreviated to Mincle), is a member of the C-type lectin superfamily encoded by the gene CLEC4E. It is a pattern recognition receptor that can recognize glycolipids including mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM).[1] [2] 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. Upon activation by cord factor, Mincle binds the Fc receptor FcRγ and Syk. Cord factor also binds and activates the related C-type lectin MCL.[3] [4] Upon receptor stimulation is PKC-δ activated, which subsequently phosphorylates CARD9 that triggers recruitment of BCL10 and MALT1, leading to a CARD-CC/BCL10/MALT1 (CBM) signaling complex. [5] This signaling complex in turn triggers downstream recruitment of TRAF6 and NF-κB 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.[6] Cholesterol sulfate, which is present in the skin, is a cause of sterile inflammation through agonizing Mincle signalling.[7] The protein SAP130 signal through Mincle.[8] Beta-glucosylceramide, which accumulates as a result of the lysosomal storage disorder Gaucher’s disease, signals through Mincle.[9]

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.[10] Glycosyl diglycerides from various pathogenic and commensal bacteria and fungi such as Lactobacillus plantarum,[11] Streptococcus pneumoniae,[12] [13] Mycobacterium tuberculosis[14] and Malassezia sp.[15]

See also

Notes and References

  1. Moody. DB. Matsunaga, I. Mincle is a long sought receptor for mycobacterial cord factor.. Journal of Experimental Medicine. 2009. 206. 13. 2879–88. 20008525. 10.1084/jem.20092533. 2806465.
  2. Ishikawa. E. Ishikawa T . Morita YS . Toyonaga K . Yamada H . Takeuchi O . Kinoshita T . Akira S . Yoshikai Y . Yamasaki S . Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle.. Journal of Experimental Medicine. 2009. 206. 13. 2865–8. 20008526. 10.1084/jem.20091750 . 2806462.
  3. Miyake. Y . Toyonaga K . Mori D . Kakuta S . Hoshino Y . Oyamada A . Yamada H . Ono K . Suyama M . Iwakura Y . Yoshikai Y . Yamasaki S. C-type lectin MCL is an FcRγ-coupled receptor that mediates the adjuvanticity of mycobacterial cord factor.. Immunity. 2013. 38. 5 . 1050–1062. 23602766. 10.1016/j.immuni.2013.03.010. free .
  4. Richardson. Mark B.. Williams. Spencer J.. 2014-06-23. MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns. Frontiers in Immunology. 5. 288. 10.3389/fimmu.2014.00288. 1664-3224. 4066366. 25002863. free.
  5. Strasser D, Neumann K, Bergmann H, Marakalala MJ, Guler R, Rojowska A . etal. Syk kinase-coupled C-type lectin receptors engage protein kinase C-δ to elicit Card9 adaptor-mediated innate immunity. . Immunity . 2012 . 36 . 1 . 32–42 . 22265677 . 10.1016/j.immuni.2011.11.015 . 3477316 .
  6. Kiyotake . R . Oh-Hora . M . Ishikawa . E . Miyamoto . T . Ishibashi . T . Yamasaki . S . Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses. . The Journal of Biological Chemistry . 16 October 2015 . 290 . 42 . 25322–32 . 10.1074/jbc.M115.645234 . 26296894. 4646182 . free .
  7. Kostarnoy . AV . Gancheva . PG . Lepenies . B . Tukhvatulin . AI . Dzharullaeva . AS . Polyakov . NB . Grumov . DA . Egorova . DA . Kulibin . AY . Bobrov . MA . Malolina . EA . Zykin . PA . Soloviev . AI . Riabenko . E . Maltseva . DV . Sakharov . DA . Tonevitsky . AG . Verkhovskaya . LV . Logunov . DY . Naroditsky . BS . Gintsburg . AL . Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate. . Proceedings of the National Academy of Sciences of the United States of America . 28 March 2017 . 114 . 13 . E2758–E2765 . 10.1073/pnas.1611665114 . 28292894. 5380039 . 2017PNAS..114E2758K . free .
  8. Yamasaki . S . Ishikawa . E . Sakuma . M . Hara . H . Ogata . K . Saito . T . Mincle is an ITAM-coupled activating receptor that senses damaged cells. . Nature Immunology . October 2008 . 9 . 10 . 1179–88 . 10.1038/ni.1651 . 18776906. 205361789 .
  9. Nagata. Masahiro. Izumi. Yoshihiro. Ishikawa. Eri. Kiyotake. Ryoko. Doi. Rieko. Iwai. Satoru. Omahdi. Zakaria. Yamaji. Toshiyuki. Miyamoto. Tomofumi. 18 April 2017. Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity. Proceedings of the National Academy of Sciences of the United States of America. 114. 16. E3285–E3294. 10.1073/pnas.1618133114. 1091-6490. 5402399. 28373578. 2017PNAS..114E3285N . free.
  10. van der Peet. PL. Gunawan. C. Torigoe. S. Yamasaki. S. Williams. Spencer J. Corynomycolic acid-containing glycolipids signal through the pattern recognition receptor Mincle. Chem. Commun.. 2015. 51. 24. 5100–5103. 10.1039/c5cc00085h. 25714652.
  11. Shah. S . Nagata M . Yamasaki D . Williams SJ . Total synthesis of a cyclopropane-fatty acid α-glucosyl diglyceride from Lactobacillus plantarum and identification of its ability to signal through Mincle.. Chemical Communications. 2016. 52. 72 . 10902–1065. 27533919 . 10.1039/C6CC05631H.
  12. Behler-Janbeck . F . Takano . T . Maus . R . Stolper . J . Jonigk . D . Tort Tarrés . M . Fuehner . T . Prasse . A . Welte . T . Timmer . MS . Stocker . BL . Nakanishi . Y . Miyamoto . T . Yamasaki . S . Maus . UA . C-type Lectin Mincle Recognizes Glucosyl-diacylglycerol of Streptococcus pneumoniae and Plays a Protective Role in Pneumococcal Pneumonia. . PLOS Pathogens . December 2016 . 12 . 12 . e1006038 . 10.1371/journal.ppat.1006038 . 27923071. 5140071 . free .
  13. Imai . T . Matsumura . T . Mayer-Lambertz . S . Wells . CA . Ishikawa . E . Butcher . SK . Barnett . TC . Walker . MJ . Imamura . A . Ishida . H . Ikebe . T . Miyamoto . T . Ato . M . Ohga . S . Lepenies . B . van Sorge . NM . Yamasaki . S . Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection. . Proceedings of the National Academy of Sciences of the United States of America . 6 November 2018 . 115 . 45 . E10662–E10671 . 10.1073/pnas.1809100115 . 30352847. 6233082 . 2018PNAS..11510662I . free .
  14. Richardson MB, S, S, SJ.. MB. Torigoe. S. Yamasaki. S. Williams. SJ. Mycobacterium tuberculosis β-gentiobiosyl diacylglycerides signal through the pattern recognition receptor Mincle: total synthesis and structure activity relationships. Chem. Commun.. 2015. 51. 81. 15027–30. 10.1039/c5cc04773k. 26310657.
  15. Ishikawa . T . Itoh . F . Yoshida . S . Saijo . S . Matsuzawa . T . Gonoi . T . Saito . T . Okawa . Y . Shibata . N . Miyamoto . T . Yamasaki . S . Identification of distinct ligands for the C-type lectin receptors Mincle and Dectin-2 in the pathogenic fungus Malassezia. . Cell Host & Microbe . 17 April 2013 . 13 . 4 . 477–88 . 10.1016/j.chom.2013.03.008 . 23601109. free .

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