Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease
Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positi...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.1058602/full |
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| author | Natallia Makarava Natallia Makarava Elizaveta Katorcha Elizaveta Katorcha Jennifer Chen-Yu Chang Jennifer Chen-Yu Chang Joseph T. Y. Lau Ilia V. Baskakov Ilia V. Baskakov |
| author_facet | Natallia Makarava Natallia Makarava Elizaveta Katorcha Elizaveta Katorcha Jennifer Chen-Yu Chang Jennifer Chen-Yu Chang Joseph T. Y. Lau Ilia V. Baskakov Ilia V. Baskakov |
| author_sort | Natallia Makarava |
| collection | DOAJ |
| description | Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. We found that a global knockout of ST6Gal1 in mice significantly reduces the α2-6 sialylation of the brain parenchyma, as determined by staining with Sambucus Nigra agglutinin. However, the sialylation of PrPSc remained stable and the incubation time to disease increased only modestly in ST6Gal1 knockout mice (ST6Gal1-KO). A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2. |
| first_indexed | 2024-04-11T08:13:35Z |
| format | Article |
| id | doaj.art-49a37e0a0d1945ac9eb16608572bfc63 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-11T08:13:35Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-49a37e0a0d1945ac9eb16608572bfc632022-12-22T04:35:14ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-11-01910.3389/fmolb.2022.10586021058602Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion diseaseNatallia Makarava0Natallia Makarava1Elizaveta Katorcha2Elizaveta Katorcha3Jennifer Chen-Yu Chang4Jennifer Chen-Yu Chang5Joseph T. Y. Lau6Ilia V. Baskakov7Ilia V. Baskakov8Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD, United StatesDepartment of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, United StatesCenter for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD, United StatesDepartment of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, United StatesCenter for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD, United StatesDepartment of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, United StatesDepartment of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United StatesCenter for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD, United StatesDepartment of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, United StatesPrion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. We found that a global knockout of ST6Gal1 in mice significantly reduces the α2-6 sialylation of the brain parenchyma, as determined by staining with Sambucus Nigra agglutinin. However, the sialylation of PrPSc remained stable and the incubation time to disease increased only modestly in ST6Gal1 knockout mice (ST6Gal1-KO). A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2.https://www.frontiersin.org/articles/10.3389/fmolb.2022.1058602/fullprionprion diseasesN-glycosylationsialic acidsialyltransferasesST6GAL1 |
| spellingShingle | Natallia Makarava Natallia Makarava Elizaveta Katorcha Elizaveta Katorcha Jennifer Chen-Yu Chang Jennifer Chen-Yu Chang Joseph T. Y. Lau Ilia V. Baskakov Ilia V. Baskakov Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease Frontiers in Molecular Biosciences prion prion diseases N-glycosylation sialic acid sialyltransferases ST6GAL1 |
| title | Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease |
| title_full | Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease |
| title_fullStr | Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease |
| title_full_unstemmed | Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease |
| title_short | Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease |
| title_sort | deficiency in st6gal1 one of the two α2 6 sialyltransferases has only a minor effect on the pathogenesis of prion disease |
| topic | prion prion diseases N-glycosylation sialic acid sialyltransferases ST6GAL1 |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.1058602/full |
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