Genetics of Glycosylation in Mammalian Development and Disease

Overview

Journal Nat Rev Genet

Specialty Genetics

Date 2024 May 9

PMID 38724711

Authors

Pamela Stanley

Affiliations

Soon will be listed here.

Abstract

Glycosylation of proteins and lipids in mammals is essential for embryogenesis and the development of all tissues. Analyses of glycosylation mutants in cultured mammalian cells and model organisms have been key to defining glycosylation pathways and the biological functions of glycans. More recently, applications of genome sequencing have revealed the breadth of rare congenital disorders of glycosylation in humans and the influence of genetics on the synthesis of glycans relevant to infectious diseases, cancer progression and diseases of the immune system. This improved understanding of glycan synthesis and functions is paving the way for advances in the diagnosis and treatment of glycosylation-related diseases, including the development of glycoprotein therapeutics through glycosylation engineering.

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References

Takahashi M, Hasegawa Y, Maeda K, Kitano M, Taniguchi N . Role of glycosyltransferases in carcinogenesis; growth factor signaling and EMT/MET programs. Glycoconj J. 2022; 39(2):167-176. PMC: 8795723. DOI: 10.1007/s10719-022-10041-3. View

Tan J, Dunn J, Jaeken J, SCHACHTER H . Mutations in the MGAT2 gene controlling complex N-glycan synthesis cause carbohydrate-deficient glycoprotein syndrome type II, an autosomal recessive disease with defective brain development. Am J Hum Genet. 1996; 59(4):810-7. PMC: 1914797. View

Radovani B, Gudelj I . N-Glycosylation and Inflammation; the Not-So-Sweet Relation. Front Immunol. 2022; 13:893365. PMC: 9272703. DOI: 10.3389/fimmu.2022.893365. View

Grzesik K, Janik M, Hoja-Lukowicz D . The hidden potential of glycomarkers: Glycosylation studies in the service of cancer diagnosis and treatment. Biochim Biophys Acta Rev Cancer. 2023; 1878(3):188889. DOI: 10.1016/j.bbcan.2023.188889. View

Ninagawa S, George G, Mori K . Mechanisms of productive folding and endoplasmic reticulum-associated degradation of glycoproteins and non-glycoproteins. Biochim Biophys Acta Gen Subj. 2020; 1865(3):129812. DOI: 10.1016/j.bbagen.2020.129812. View

Liu Y, Yen H, Chen C, Chen C, Cheng P, Juan Y . Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells. Proc Natl Acad Sci U S A. 2011; 108(28):11332-7. PMC: 3136320. DOI: 10.1073/pnas.1107385108. View

Yen H, Liu Y, Chen N, Tsai C, Wang Y, Chen Y . Effect of sialylation on EGFR phosphorylation and resistance to tyrosine kinase inhibition. Proc Natl Acad Sci U S A. 2015; 112(22):6955-60. PMC: 4460513. DOI: 10.1073/pnas.1507329112. View

Saiki W, Ma C, Okajima T, Takeuchi H . Current Views on the Roles of -Glycosylation in Controlling Notch-Ligand Interactions. Biomolecules. 2021; 11(2). PMC: 7922208. DOI: 10.3390/biom11020309. View

Paulson J, Colley K . Glycosyltransferases. Structure, localization, and control of cell type-specific glycosylation. J Biol Chem. 1989; 264(30):17615-8. View

10.

Slavov N . Single-cell proteomics: quantifying post-transcriptional regulation during development with mass-spectrometry. Development. 2023; 150(13). PMC: 10323229. DOI: 10.1242/dev.201492. View

11.

Huang Y, Aoki K, Akase S, Ishihara M, Liu Y, Yang G . Global mapping of glycosylation pathways in human-derived cells. Dev Cell. 2021; 56(8):1195-1209.e7. PMC: 8086148. DOI: 10.1016/j.devcel.2021.02.023. View

12.

Dworkin L, Clausen H, Joshi H . Applying transcriptomics to studyglycosylation at the cell type level. iScience. 2022; 25(6):104419. PMC: 9156939. DOI: 10.1016/j.isci.2022.104419. View

13.

York W, Mazumder R, Ranzinger R, Edwards N, Kahsay R, Aoki-Kinoshita K . GlyGen: Computational and Informatics Resources for Glycoscience. Glycobiology. 2019; 30(2):72-73. PMC: 7335483. DOI: 10.1093/glycob/cwz080. View

14.

Sosicka P, Ng B, Pepi L, Shajahan A, Wong M, Scott D . Origin of cytoplasmic GDP-fucose determines its contribution to glycosylation reactions. J Cell Biol. 2022; 221(10). PMC: 9441714. DOI: 10.1083/jcb.202205038. View

15.

DSouza Z, Sumya F, Khakurel A, Lupashin V . Getting Sugar Coating Right! The Role of the Golgi Trafficking Machinery in Glycosylation. Cells. 2021; 10(12). PMC: 8699264. DOI: 10.3390/cells10123275. View

16.

Aryal R, Ju T, Cummings R . The endoplasmic reticulum chaperone Cosmc directly promotes in vitro folding of T-synthase. J Biol Chem. 2009; 285(4):2456-62. PMC: 2807302. DOI: 10.1074/jbc.M109.065169. View

17.

Ju T, Cummings R . A unique molecular chaperone Cosmc required for activity of the mammalian core 1 beta 3-galactosyltransferase. Proc Natl Acad Sci U S A. 2002; 99(26):16613-8. PMC: 139192. DOI: 10.1073/pnas.262438199. View

18.

Pechincha C, Groessl S, Kalis R, de Almeida M, Zanotti A, Wittmann M . Lysosomal enzyme trafficking factor LYSET enables nutritional usage of extracellular proteins. Science. 2022; 378(6615):eabn5637. DOI: 10.1126/science.abn5637. View

19.

Yamaji T, Sekizuka T, Tachida Y, Sakuma C, Morimoto K, Kuroda M . A CRISPR Screen Identifies LAPTM4A and TM9SF Proteins as Glycolipid-Regulating Factors. iScience. 2019; 11:409-424. PMC: 6348303. DOI: 10.1016/j.isci.2018.12.039. View

20.

Tian S, Muneeruddin K, Choi M, Tao L, Bhuiyan R, Ohmi Y . Genome-wide CRISPR screens for Shiga toxins and ricin reveal Golgi proteins critical for glycosylation. PLoS Biol. 2018; 16(11):e2006951. PMC: 6258472. DOI: 10.1371/journal.pbio.2006951. View