Platelets and Defective N-Glycosylation

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Aug 13

PMID 32781578

Citations 13

Authors

Elmina Mammadova-Bach

Jaak Jaeken

Thomas Gudermann

Attila Braun

Affiliations

Soon will be listed here.

Abstract

N-glycans are covalently linked to an asparagine residue in a simple acceptor sequence of proteins, called a sequon. This modification is important for protein folding, enhancing thermodynamic stability, and decreasing abnormal protein aggregation within the endoplasmic reticulum (ER), for the lifetime and for the subcellular localization of proteins besides other functions. Hypoglycosylation is the hallmark of a group of rare genetic diseases called congenital disorders of glycosylation (CDG). These diseases are due to defects in glycan synthesis, processing, and attachment to proteins and lipids, thereby modifying signaling functions and metabolic pathways. Defects in N-glycosylation and O-glycosylation constitute the largest CDG groups. Clotting and anticlotting factor defects as well as a tendency to thrombosis or bleeding have been described in CDG patients. However, N-glycosylation of platelet proteins has been poorly investigated in CDG. In this review, we highlight normal and deficient N-glycosylation of platelet-derived molecules and discuss the involvement of platelets in the congenital disorders of N-glycosylation.

Citing Articles

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References

Jackson S . Arterial thrombosis--insidious, unpredictable and deadly. Nat Med. 2011; 17(11):1423-36. DOI: 10.1038/nm.2515. View

Li F, Chaigne-Delalande B, Su H, Uzel G, Matthews H, Lenardo M . XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus. Blood. 2014; 123(14):2148-52. PMC: 3975255. DOI: 10.1182/blood-2013-11-538686. View

Dietrich A, Mederos Y Schnitzler M, Emmel J, Kalwa H, Hofmann T, Gudermann T . N-linked protein glycosylation is a major determinant for basal TRPC3 and TRPC6 channel activity. J Biol Chem. 2003; 278(48):47842-52. DOI: 10.1074/jbc.M302983200. View

Kunicki T, Cheli Y, Moroi M, Furihata K . The influence of N-linked glycosylation on the function of platelet glycoprotein VI. Blood. 2005; 106(8):2744-9. PMC: 1895313. DOI: 10.1182/blood-2005-04-1454. View

Nurden A . Clinical significance of altered collagen-receptor functioning in platelets with emphasis on glycoprotein VI. Blood Rev. 2019; 38:100592. DOI: 10.1016/j.blre.2019.100592. View

Samih N, Hovsepian S, Notel F, Prorok M, Zattara-Cannoni H, Mathieu S . The impact of N- and O-glycosylation on the functions of Glut-1 transporter in human thyroid anaplastic cells. Biochim Biophys Acta. 2003; 1621(1):92-101. DOI: 10.1016/s0304-4165(03)00050-3. View

Mo X, Nguyen N, McEwan P, Zheng X, Lopez J, Emsley J . Binding of platelet glycoprotein Ibbeta through the convex surface of leucine-rich repeats domain of glycoprotein IX. J Thromb Haemost. 2009; 7(9):1533-40. PMC: 3046765. DOI: 10.1111/j.1538-7836.2009.03536.x. View

Fidler T, Campbell R, Funari T, Dunne N, Balderas Angeles E, Middleton E . Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function. Cell Rep. 2017; 20(4):881-894. PMC: 5600478. DOI: 10.1016/j.celrep.2017.06.083. View

Ma X, Li Y, Kondo Y, Shi H, Han J, Jiang Y . Slc35a1 deficiency causes thrombocytopenia due to impaired megakaryocytopoiesis and excessive platelet clearance in the liver. Haematologica. 2020; 106(3):759-769. PMC: 7927894. DOI: 10.3324/haematol.2019.225987. View

10.

Zhou L, Qian Y, Zhang X, Ruan Y, Ren S, Gu J . Elucidation of differences in N-glycosylation between different molecular weight forms of recombinant CLEC-2 by LC MALDI tandem MS. Carbohydr Res. 2014; 402:180-8. DOI: 10.1016/j.carres.2014.07.005. View

11.

Isordia-Salas I, Pixley R, Parekh H, Kunapuli S, Li F, Stadnicki A . The mutation Ser511Asn leads to N-glycosylation and increases the cleavage of high molecular weight kininogen in rats genetically susceptible to inflammation. Blood. 2003; 102(8):2835-42. DOI: 10.1182/blood-2003-02-0661. View

12.

Quinsey N, Greedy A, Bottomley S, Whisstock J, Pike R . Antithrombin: in control of coagulation. Int J Biochem Cell Biol. 2003; 36(3):386-9. DOI: 10.1016/s1357-2725(03)00244-9. View

13.

Mammadova-Bach E, Nagy M, Heemskerk J, Nieswandt B, Braun A . Store-operated calcium entry in thrombosis and thrombo-inflammation. Cell Calcium. 2018; 77:39-48. DOI: 10.1016/j.ceca.2018.11.005. View

14.

Kramer P, Ravi S, Chacko B, Johnson M, Darley-Usmar V . A review of the mitochondrial and glycolytic metabolism in human platelets and leukocytes: implications for their use as bioenergetic biomarkers. Redox Biol. 2014; 2:206-10. PMC: 3909784. DOI: 10.1016/j.redox.2013.12.026. View

15.

Hofmann T, Obukhov A, Schaefer M, Harteneck C, Gudermann T, Schultz G . Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature. 1999; 397(6716):259-63. DOI: 10.1038/16711. View

16.

Hoffmeister K, Felbinger T, Falet H, Denis C, Bergmeier W, Mayadas T . The clearance mechanism of chilled blood platelets. Cell. 2003; 112(1):87-97. DOI: 10.1016/s0092-8674(02)01253-9. View

17.

Clemetson J, Polgar J, Magnenat E, Wells T, Clemetson K . The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to FcalphaR and the natural killer receptors. J Biol Chem. 1999; 274(41):29019-24. DOI: 10.1074/jbc.274.41.29019. View

18.

Dietrich A, Gudermann T . TRPC6: physiological function and pathophysiological relevance. Handb Exp Pharmacol. 2014; 222:157-88. DOI: 10.1007/978-3-642-54215-2_7. View

19.

Chaigne-Delalande B, Li F, OConnor G, Lukacs M, Jiang P, Zheng L . Mg2+ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infection through NKG2D. Science. 2013; 341(6142):186-91. PMC: 3894782. DOI: 10.1126/science.1240094. View

20.

Heijnen H, Oorschot V, Sixma J, Slot J, James D . Thrombin stimulates glucose transport in human platelets via the translocation of the glucose transporter GLUT-3 from alpha-granules to the cell surface. J Cell Biol. 1997; 138(2):323-30. PMC: 2138201. DOI: 10.1083/jcb.138.2.323. View