Simultaneous characterization of sequence polymorphisms, glycosylation and phosphorylation of fibrinogen in a direct analysis by LC–MS

Nagel, Tim; Meyer, Bernd

doi:10.1016/j.bbapap.2014.09.021

Cited by 17 publications

(16 citation statements)

References 37 publications

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“…As Plt Slc35a1 -/mice have normal sialylation in cells including hematopoietic cells other than megakyocytes/platelets, we hypothesized that residual sialylation in Slc35a1 -/platelets is caused by exogenous plasma sialylated molecules, such as fibrinogen and IgG that are abundant in the plasma and known to be sialylated, internalized by circulating platelets. [28][29][30][31] In addition, exogenous IgG is also commonly found on the surface of platelets (PAIgG). 30,31 This can be reflected in the fact that the relative ratios of singly to doubly-sialyated glycoforms remained consistent to each other in the WT and Slc35a1 -/platelets, rather than the number of doubly-sialyated glycoforms decreasing in addition to the singly-sialyated and non-sialyated species increasing in incomplete Slc35a1 -/platelets.…”

Section: Slc35a1 -/Platelets and Megakaryocytes Are Deficient In Sialmentioning

confidence: 99%

Slc35a1 deficiency causes thrombocytopenia due to impaired megakaryocytopoiesis and excessive platelet clearance in the liver

Shi

et al. 2020

haematol

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Sialic acid is a common terminal residue of glycans on proteins and acidic sphingolipids such as gangliosides with important biological functions. The sialylation process is controlled by more than 20 different sialyltransferases, many of which exhibit overlapping functions. Thus, it is difficult to determine the overall biological function of sialylation by targeted deletion of individual sialyltransferase. To address this question, we established a mouse line with the Slc35a1 gene flanked by loxP sites. Slc35a1 encodes the CMP-sialic acid transporter that transports CMP-sialic acid from cytoplasm into the Golgi apparatus for sialylation. Here we report our study regarding the role of sialylation on megakaryocytes and platelets using a mouse line with significantly reduced sialylation in megakaryocytes and platelets (Plt Slc35a1-/-). The major phenotype of Plt Slc35a1-/- mice was thrombocytopenia. The number of bone marrow megakaryocytes in Plt Slc35a1-/- mice was reduced, and megakaryocyte maturation was also impaired. In addition, an increased number of desialylated platelets was cleared by Kupffer cells in the liver of Plt Slc35a1-/- mice. This study provides new insights into the role of sialylation in platelet homeostasis and the mechanisms of thrombocytopenia in diseases associated with platelet desialylation, such as immune thrombocytopenic purpura and a rare congenital disorder of glycosylation (CDG), SLC35A1-CDG, which is caused by SLC35A1 mutations.

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Section: Slc35a1 -/Platelets and Megakaryocytes Are Deficient In Sialmentioning

confidence: 99%

Slc35a1 deficiency causes thrombocytopenia due to impaired megakaryocytopoiesis and excessive platelet clearance in the liver

Shi

et al. 2020

haematol

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“…Posttranslational modifications including glycosylation, phosphorylation, and sequence polymorphisms of human fibrinogen, which was isolated and separated into the Aα‐, Bβ‐, and γ‐subunits by RPLC, were identified simultaneously by top‐down MS . Two coding single nucleotide polymorphisms on the Aα‐ and Bβ‐subunit were recognized, indicating both heterogeneous and homogeneous sites.…”

Section: New Glycomics and Glycoproteomics Biomedical Applicationsmentioning

confidence: 99%

Recent advances in mass spectrometric analysis of glycoproteins

et al. 2016

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Glycosylation is one of the most common post-translational modifications of proteins and plays essential roles in various biological processes, including protein folding, host-pathogen interaction, immune response, and inflammation and aberrant protein glycosylation is a well-known event in various disease states including cancer. As a result, it is critical to develop rapid and sensitive methods for the analysis of abnormal glycoproteins associated with diseases. Mass spectrometry in conjugation with different separation methods, such as capillary electrophoresis, ion mobility, and high performance liquid chromatography, has become a popular tool for glycoprotein analysis, providing highly informative fragments for structural identification of glycoproteins. This review provides an overview of the developments and accomplishments in the field of glycomics and glycoproteomics reported between 2014 and 2016.

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“…The effect of Arg448Lys polymorphism on fibrinogen is still ambiguous. It is related to fibrinogen level and atherothrombotic disease risk according to some previous studies [18,19], whereas there is also a study showing that it has no influence on the function or structure of fibrinogen [20]. So it may play its role through other ways than directly disrupting the gross protein structure.…”

Section: Discussionmentioning

confidence: 93%

Two symptomatic cases of dysfibrinogenemia in China

Bin

Fang²,

Ou³

et al. 2015

Blood Coagulation &Amp; Fibrinolysis

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The aim of this study was to investigate causative mutations of two unrelated symptomatic Chinese children with dysfibrinogenemia and their family members.Fibrinogen genes, including FGA, FGB and FGG of all participants were PCR-amplified, followed by direct sequencing. Precipitated plasma fibrinogen of some family members was analyzed by western blotting, fibrin polymerization and scanning electron microscopy (SEM).Proband 1 associated with frequent epistaxis was identified to harbor a heterozygous Arg275Cys mutation in FGG, along with a polymorphism Arg448Lys in FGB. Proband 2 with apparently prolonged thrombin time and very low functional fibrinogen had undergone both spontaneous intracranial hemorrhages and deep venous thrombosis. Sequencing of all proximal promoters, coding regions, introns and 3'-untranslated region using genomic DNA of Proband 2 yielded no mutation in three fibrinogen genes. Western blotting of this patient's precipitated plasma fibrinogen detected no truncated protein. Fibrinogen polymerization curve showed prolonged lag phase and severely decreased final turbidity, and SEM observations of fibrin clots made from Proband 2 revealed an abnormal sponge-like mass with large pores. We speculate that other underlying mechanisms responsible for dysfibrinogenemia such as abnormal posttranscriptional processing or posttranslational modification, which are independent of detectable mutations in the genomic DNA sequence, may exist.

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Simultaneous characterization of sequence polymorphisms, glycosylation and phosphorylation of fibrinogen in a direct analysis by LC–MS

Cited by 17 publications

References 37 publications

Slc35a1 deficiency causes thrombocytopenia due to impaired megakaryocytopoiesis and excessive platelet clearance in the liver

Slc35a1 deficiency causes thrombocytopenia due to impaired megakaryocytopoiesis and excessive platelet clearance in the liver

Recent advances in mass spectrometric analysis of glycoproteins

Two symptomatic cases of dysfibrinogenemia in China

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