Abstract
Notch signaling occurs following the activation of membrane-bound Notch receptors by canonical Notch ligands expressed in neighboring cells. It is a fundamental requirement for the regulation of cell fate decisions during organellar differentiation in mammals. The extracellular domain of Notch receptors comprises numerous epidermal growth factor-like (EGF) repeats, many of which are modified by glycans O-linked to Ser or Thr at specific consensus sites. This chapter will summarize the nature and functions of O-Fucose, O-Glucose, O-GlcNAc, and O-GalNAc glycans in mammalian cells, mouse development, and human disease. Congenital diseases that arise from reduced addition of O-glycans reveal the importance of these modifications for Notch signaling.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alfaro JF, Gong CX, Monroe ME, Aldrich JT, Clauss TR, Purvine SO et al (2012) Tandem mass spectrometry identifies many mouse brain O-GlcNAcylated proteins including EGF domain-specific O-GlcNAc transferase targets. Proc Natl Acad Sci U S A 109:7280–7285
Basmanav FB, Oprisoreanu AM, Pasternack SM, Thiele H, Fritz G, Wenzel J et al (2014) Mutations in POGLUT1, encoding protein O-glucosyltransferase 1, cause autosomal-dominant Dowling-Degos disease. Am J Hum Genet 94:135–143
Boskovski MT, Yuan S, Pedersen NB, Goth CK, Makova S, Clausen H et al (2013) The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality. Nature 504:456–459
Cohen I, Silberstein E, Perez Y, Landau D, Elbedour K, Langer Y et al (2013) Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT, encoding an EGF domain-specific O-GlcNAc transferase. Eur J Hum Genet 22(3):374–378
Fernandez-Valdivia R, Takeuchi H, Samarghandi A, Lopez M, Leonardi J, Haltiwanger RS et al (2011) Regulation of mammalian Notch signaling and embryonic development by the protein O-glucosyltransferase Rumi. Development 138:1925–1934
Hansske B, Thiel C, Lubke T, Hasilik M, Honing S, Peters V et al (2002) Deficiency of UDP-galactose:N-acetylglucosamine beta-1,4-galactosyltransferase I causes the congenital disorder of glycosylation type IId. J Clin Invest 109:725–733
Jafar-Nejad H, Leonardi J, Fernandez-Valdivia R (2010) Role of glycans and glycosyltransferases in the regulation of Notch signaling. Glycobiology 20:931–949
Kopan R (2012) Notch signaling. Cold Spring Harb Perspect Biol 4:1–10
Li M, Cheng R, Liang J, Yan H, Zhang H, Yang L et al (2013) Mutations in POFUT1, encoding protein O-fucosyltransferase 1, cause generalized Dowling-Degos disease. Am J Hum Genet 92:895–903
Rana NA, Haltiwanger RS (2011) Fringe benefits: functional and structural impacts of O-glycosylation on the extracellular domain of Notch receptors. Curr Opin Struct Biol 21:583–589
Sakaidani Y, Nomura T, Matsuura A, Ito M, Suzuki E, Murakami K et al (2011) O-Linked-N-acetylglucosamine on extracellular protein domains mediates epithelial cell-matrix interactions. Nat Commun 2:583
Shaheen R, Aglan M, Keppler-Noreuil K, Faqeih E, Ansari S, Horton K et al (2013) Mutations in EOGT confirm the genetic heterogeneity of autosomal-recessive Adams-Oliver syndrome. Am J Hum Genet 92:598–604
Shi S, Stanley P (2003) Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways. Proc Natl Acad Sci U S A 100(9):5234–5239
Sparrow DB, Chapman G, Wouters MA, Whittock NV, Ellard S, Fatkin D et al (2006) Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype. Am J Hum Genet 78:28–37
Stanley P, Okajima T (2010) Roles of glycosylation in Notch signaling. Curr Top Dev Biol 92:131–164
Yuan JS, Kousis PC, Suliman S, Visan I, Guidos CJ (2010) Functions of notch signaling in the immune system: consensus and controversies. Annu Rev Immunol 28:343–365
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Japan
About this entry
Cite this entry
Stanley, P. (2014). O-Glycans in Mammalian Notch Signaling. In: Endo, T., Seeberger, P., Hart, G., Wong, CH., Taniguchi, N. (eds) Glycoscience: Biology and Medicine. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54836-2_165-1
Download citation
DOI: https://doi.org/10.1007/978-4-431-54836-2_165-1
Received:
Accepted:
Published:
Publisher Name: Springer, Tokyo
Online ISBN: 978-4-431-54836-2
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences