Skip to main content
SpringerLink
Log in

Introduction to Notch Signaling

  • Protocol
  • First Online:
Notch Signaling

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1187))

Abstract

Notch signaling is probably the most widely used intercellular communication pathway. The Notch mutant in the fruit fly Drosophila melanogaster was isolated about 100 years ago at the dawn of genetics. Since then, research on Notch and its related genes in flies, worms, mice, and human has led to the establishment of an evolutionarily conserved signaling pathway, the Notch signaling pathway. In the past few decades, molecular cloning of the Notch signaling components as well as genetic, cell biological, biochemical, structural, and bioinformatic approaches have uncovered the basic molecular logic of the pathway. In addition, genetic screens and systems approaches have led to the expansion of the list of genes that interact and fine-tune the pathway in a context specific manner. Furthermore, recent human genetic and genomic studies have led to the discovery that Notch plays a role in numerous diseases such as congenital disorders, stroke, and especially cancer. Pharmacological studies are actively pursuing key components of the pathway as drug targets for potential therapy. In this chapter, we will provide a brief historical overview of Notch signaling research and discuss the basic principles of Notch signaling, focusing on the unique features of this pathway when compared to other signaling pathways. Further studies to understand and manipulate Notch signaling in vivo in model organisms and in clinical settings will require a combination of a number of different approaches that are discussed throughout this book.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Morgan TH, Bridges CB (1916) Sex-linked inheritance in Drosophila. Carnegie Inst Wash Publ 237:1–88

    Google Scholar 

  2. Morgan TH (1917) The theory of the gene. Am Nat 51:513–544

    Google Scholar 

  3. Dexter JS (1914) The analysis of a case of continuous variation in Drosophila by a study of its linkage relations. Am Nat 48:712–758

    Google Scholar 

  4. Mohr OL (1919) Character changes caused by mutation of an entire region of a chromosome in Drosophila. Genetics 4:275–282

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Lindsley DL, Zimm GG (1992) The genome of Drosophila melanogaster. Academic, Waltham

    Google Scholar 

  6. Poulson DF (1937) Chromosomal Deficiencies and the Embryonic Development of Drosophila Melanogaster. Proc Natl Acad Sci U S A. 23(3):133–7

    Google Scholar 

  7. Poulson DF (1936) Chromosome deficiencies and embryonic development. Ph.D. thesis, Caltech, CA

    Google Scholar 

  8. Lehmann R, Jimenez F, Dietrich U, Campos-Ortega JA (1983) On the phenotype and development of mutants of early neurogenesis in Drosophila melanogaster. Rouxs Arch Dev Biol 192:62–74

    Google Scholar 

  9. Lehmann R, Dietrich U, Jiménez F, Campos-Ortega JA (1981) Mutations of early neurogenesis in Drosophila. Rouxs Arch Dev Biol 190:226–229

    Google Scholar 

  10. Fortini ME, Artavanis-Tsakonas S (1994) The suppressor of hairless protein participates in notch receptor signaling. Cell 79:273–282

    CAS  PubMed  Google Scholar 

  11. Fleming RJ, Scottgale TN, Diederich RJ et al (1990) The gene Serrate encodes a putative EGF-like transmembrane protein essential for proper ectodermal development in Drosophila melanogaster. Genes Dev 4:2188–2201

    CAS  PubMed  Google Scholar 

  12. Artavanis-Tsakonas S, Muskavitch MA, Yedvobnick B (1983) Molecular cloning of Notch, a locus affecting neurogenesis in Drosophila melanogaster. Proc Natl Acad Sci U S A 80:1977–1981

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Kidd S, Lockett TJ, Young MW (1983) The Notch locus of Drosophila melanogaster. Cell 34:421–433

    CAS  PubMed  Google Scholar 

  14. Wharton KA, Johansen KM, Xu T et al (1985) Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing EGF-like repeats. Cell 43:567–581

    CAS  PubMed  Google Scholar 

  15. Kidd S, Kelley MR, Young MW (1986) Sequence of the notch locus of Drosophila melanogaster: relationship of the encoded protein to mammalian clotting and growth factors. Mol Cell Biol 6:3094–3108

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Priess JR, Schnabel H, Schnabel R (1987) The glp-1 locus and cellular interactions in early C. elegans embryos. Cell 51:601–611

    CAS  PubMed  Google Scholar 

  17. Austin J, Kimble J (1987) glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans. Cell 51:589–599

    CAS  PubMed  Google Scholar 

  18. Greenwald I (1987) The lin-12 locus of Caenorhabditis elegans. Bioessays 6:70–73

    CAS  PubMed  Google Scholar 

  19. Coffman C, Harris W, Kintner C (1990) Xotch, the Xenopus homolog of Drosophila notch. Science 249:1438–1441

    CAS  PubMed  Google Scholar 

  20. Ellisen LW, Bird J, West DC et al (1991) TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66:649–661

    CAS  PubMed  Google Scholar 

  21. Greenwald I, Rubin GM (1992) Making a difference: the role of cell-cell interactions in establishing separate identities for equivalent cells. Cell 68:271–281

    CAS  PubMed  Google Scholar 

  22. Fortini ME, Artavanis-Tsakonas S (1993) Notch: neurogenesis is only part of the picture. Cell 75:1245–1247

    CAS  PubMed  Google Scholar 

  23. Artavanis-Tsakonas S, Matsuno K, Fortini ME (1995) Notch signaling. Science 268:225–232

    CAS  PubMed  Google Scholar 

  24. Francis R, McGrath G, Zhang J et al (2002) aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation. Dev Cell 3:85–97

    CAS  PubMed  Google Scholar 

  25. Goutte C, Hepler W, Mickey KM et al (2000) aph-2 encodes a novel extracellular protein required for GLP-1-mediated signaling. Development 127:2481–2492

    CAS  PubMed  Google Scholar 

  26. Goutte C, Tsunozaki M, Hale VA et al (2002) APH-1 is a multipass membrane protein essential for the Notch signaling pathway in Caenorhabditis elegans embryos. Proc Natl Acad Sci U S A 99:775–779

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Levitan D, Greenwald I (1995) Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer’s disease gene. Nature 377:351–354

    CAS  PubMed  Google Scholar 

  28. Coffman CR, Skoglund P, Harris WA et al (1993) Expression of an extracellular deletion of Xotch diverts cell fate in Xenopus embryos. Cell 73:659–671

    CAS  PubMed  Google Scholar 

  29. Kopan R, Nye JS, Weintraub H (1994) The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD. Development 120:2385–2396

    CAS  PubMed  Google Scholar 

  30. Struhl G, Fitzgerald K, Greenwald I (1993) Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo. Cell 74:331–345

    CAS  PubMed  Google Scholar 

  31. Schroeter EH, Kisslinger JA, Kopan R (1998) Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 393:382–386

    CAS  PubMed  Google Scholar 

  32. De Strooper B, Annaert W, Cupers P et al (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398:518–522

    PubMed  Google Scholar 

  33. Kovall RA, Blacklow SC (2010) Mechanistic insights into Notch receptor signaling from structural and biochemical studies. Curr Top Dev Biol 92:31–71

    CAS  PubMed  Google Scholar 

  34. Artavanis-Tsakonas S, Muskavitch MA (2010) Notch: the past, the present, and the future. Curr Top Dev Biol 92:1–29

    CAS  PubMed  Google Scholar 

  35. Louvi A, Artavanis-Tsakonas S (2012) Notch and disease: a growing field. Semin Cell Dev Biol 23:473–480

    CAS  PubMed  Google Scholar 

  36. Koch U, Lehal R, Radtke F (2013) Stem cells living with a Notch. Development 140:689–704

    CAS  PubMed  Google Scholar 

  37. Ables JL, Breunig JJ, Eisch AJ et al (2011) Not(ch) just development: Notch signalling in the adult brain. Nat Rev Neurosci 12:269–283

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Pierfelice T, Alberi L, Gaiano N (2011) Notch in the vertebrate nervous system: an old dog with new tricks. Neuron 69:840–855

    CAS  PubMed  Google Scholar 

  39. Kopan R, Ilagan MX (2009) The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 137:216–233

    CAS  PubMed Central  PubMed  Google Scholar 

  40. D’Souza B, Meloty-Kapella L, Weinmaster G (2010) Canonical and non-canonical Notch ligands. Curr Top Dev Biol 92:73–129

    PubMed  Google Scholar 

  41. Vaessin H, Campos-Ortega JA (1987) Genetic analysis of delta: a neurogenic gene of Drosophila melanogaster. Genetics 116:433–446

    Google Scholar 

  42. McDaniell R, Warthen DM, Sanchez-Lara PA et al (2006) NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet 79:169–173

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Krebs LT, Shutter JR, Tanigaki K et al (2004) Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants. Genes Dev 18:2469–2473

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Demehri S, Turkoz A, Kopan RE (2009) Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment. Cancer Cell 16:55–66

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Nicolas M, Wolfer A, Raj K et al (2003) Notch1 functions as a tumor suppressor in mouse skin. Nat Genet 33:416–421

    CAS  PubMed  Google Scholar 

  46. Pear WS, Aster JC, Scott ML et al (1996) Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles. J Exp Med 183:2283–2291

    CAS  PubMed  Google Scholar 

  47. Weng AP, Ferrando AA, Lee W et al (2004) Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306:269–271

    CAS  PubMed  Google Scholar 

  48. Rosati E, Sabatini R, Rampino G et al (2009) Constitutively activated Notch signaling is involved in survival and apoptosis resistance of B-CLL cells. Blood 113:856–865

    CAS  PubMed  Google Scholar 

  49. Agrawal N, Frederick MJ, Pickering CR et al (2011) Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 333:1154–1157

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Wang NJ, Sanborn Z, Arnett KL et al (2011) Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma. Proc Natl Acad Sci U S A 108:17761–17766

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Stransky N, Egloff AM, Tward AD et al (2011) The mutational landscape of head and neck squamous cell carcinoma. Science 333:1157–1160

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Bray SJ (2006) Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol 7:678–689

    CAS  PubMed  Google Scholar 

  53. de Bivort BL, Guo HF, Zhong Y (2009) Notch signaling is required for activity-dependent synaptic plasticity at the Drosophila neuromuscular junction. J Neurogenet 23:395–404

    PubMed  Google Scholar 

  54. Song Q, Sun K, Shuai Y et al (2009) Suppressor of hairless is required for long-term memory formation in Drosophila. J Neurogenet 23:405–411

    CAS  PubMed  Google Scholar 

  55. Ge X, Hannan F, Xie Z et al (2004) Notch signaling in Drosophila long-term memory formation. Proc Natl Acad Sci U S A 101:10172–10176

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Presente A, Boyles RS, Serway CN et al (2004) Notch is required for long-term memory in Drosophila. Proc Natl Acad Sci U S A 101:1764–1768

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Lieber T, Kidd S, Struhl G (2011) DSL-Notch signaling in the Drosophila brain in response to olfactory stimulation. Neuron 69:468–481

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Costa RM, Honjo T, Silva AJ (2003) Learning and memory deficits in Notch mutant mice. Curr Biol 13:1348–1354

    CAS  PubMed  Google Scholar 

  59. Alberi L, Liu S, Wang Y et al (2011) Activity-induced Notch signaling in neurons requires Arc/Arg3.1 and is essential for synaptic plasticity in hippocampal networks. Neuron 69:437–444

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Conboy L, Seymour CM, Monopoli MP et al (2007) Notch signalling becomes transiently attenuated during long-term memory consolidation in adult Wistar rats. Neurobiol Learn Mem 88:342–351

    CAS  PubMed  Google Scholar 

  61. Andersson ER, Sandberg R, Lendahl U (2011) Notch signaling: simplicity in design, versatility in function. Development 138:3593–3612

    CAS  PubMed  Google Scholar 

  62. Ilagan MX, Kopan R (2007) SnapShot: notch signaling pathway. Cell 128:1246

    PubMed  Google Scholar 

  63. Heitzler P (2010) Biodiversity and noncanonical Notch signaling. Curr Top Dev Biol 92:457–481

    CAS  PubMed  Google Scholar 

  64. 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

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Munro S, Freeman M (2000) The notch signalling regulator fringe acts in the Golgi apparatus and requires the glycosyltransferase signature motif DXD. Curr Biol 10:813–820

    CAS  PubMed  Google Scholar 

  66. Moloney DJ, Panin VM, Johnston SH et al (2000) Fringe is a glycosyltransferase that modifies Notch. Nature 406:369–375

    CAS  PubMed  Google Scholar 

  67. Bruckner K, Perez L, Clausen H et al (2000) Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature 406:411–415

    CAS  PubMed  Google Scholar 

  68. Acar M, Jafar-Nejad H, Takeuchi H et al (2008) Rumi is a CAP10 domain glycosyltransferase that modifies Notch and is required for Notch signaling. Cell 132:247–258

    CAS  PubMed Central  PubMed  Google Scholar 

  69. Lee TV, Sethi MK, Leonardi J et al (2013) Negative regulation of notch signaling by xylose. PLoS Genet 9:e1003547

    CAS  PubMed Central  PubMed  Google Scholar 

  70. Logeat F, Bessia C, Brou C et al (1998) The Notch1 receptor is cleaved constitutively by a furin-like convertase. Proc Natl Acad Sci U S A 95:8108–8112

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Lake RJ, Grimm LM, Veraksa A et al (2009) In vivo analysis of the Notch receptor S1 cleavage. PLoS One 4:e6728

    PubMed Central  PubMed  Google Scholar 

  72. Gordon WR, Vardar-Ulu D, L’Heureux S et al (2009) Effects of S1 cleavage on the structure, surface export, and signaling activity of human Notch1 and Notch2. PLoS One 4:e6613

    PubMed Central  PubMed  Google Scholar 

  73. Jen WC, Wettstein D, Turner D et al (1997) The Notch ligand, X-Delta-2, mediates segmentation of the paraxial mesoderm in Xenopus embryos. Development 124:1169–1178

    CAS  PubMed  Google Scholar 

  74. Charng WL, Yamamoto S, Jaiswal M et al (2014) Drosophila Tempura, a novel protein prenyltransferase α subunit, regulates notch signaling via Rab1 and Rab11. PLoS Biol 12(1):e1001777

    PubMed Central  PubMed  Google Scholar 

  75. Giagtzoglou N, Yamamoto S, Zitserman D et al (2012) dEHBP1 controls exocytosis and recycling of Delta during asymmetric divisions. J Cell Biol 196:65–83

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Yamamoto S, Charng WL, Bellen HJ (2010) Endocytosis and intracellular trafficking of Notch and its ligands. Curr Top Dev Biol 92:165–200

    CAS  PubMed  Google Scholar 

  77. Weinmaster G, Fischer JA (2011) Notch ligand ubiquitylation: what is it good for? Dev Cell 21:134–144

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Jorissen E, De Strooper B (2010) Gamma-secretase and the intramembrane proteolysis of Notch. Curr Top Dev Biol 92:201–230

    CAS  PubMed  Google Scholar 

  79. Huenniger K, Kramer A, Soom M et al (2010) Notch1 signaling is mediated by importins alpha 3, 4, and 7. Cell Mol Life Sci 67:3187–3196

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Wharton KA, Yedvobnick B, Finnerty VG et al (1985) opa: a novel family of transcribed repeats shared by the Notch locus and other developmentally regulated loci in D. melanogaster. Cell 40:55–62

    CAS  PubMed  Google Scholar 

  81. Ramain P, Khechumian K, Seugnet L et al (2001) Novel Notch alleles reveal a Deltex-dependent pathway repressing neural fate. Curr Biol 11:1729–1738

    CAS  PubMed  Google Scholar 

  82. Fryer CJ, White JB, Jones KA (2004) Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell 16:509–520

    CAS  PubMed  Google Scholar 

  83. Borggrefe T, Liefke R (2012) Fine-tuning of the intracellular canonical Notch signaling pathway. Cell Cycle 11:264–276

    CAS  PubMed  Google Scholar 

  84. Tanigaki K, Honjo T (2010) Two opposing roles of RBP-J in Notch signaling. Curr Top Dev Biol 92:231–252

    CAS  PubMed  Google Scholar 

  85. Furriols M, Bray S (2001) A model Notch response element detects suppressor of hairless-dependent molecular switch. Curr Biol 11:60–64

    CAS  PubMed  Google Scholar 

  86. Nagel AC, Krejci A, Tenin G et al (2005) Hairless-mediated repression of notch target genes requires the combined activity of Groucho and CtBP corepressors. Mol Cell Biol 25:10433–10441

    CAS  PubMed Central  PubMed  Google Scholar 

  87. Morel V, Lecourtois M, Massiani O et al (2001) Transcriptional repression by suppressor of hairless involves the binding of a hairless-dCtBP complex in Drosophila. Curr Biol 11:789–792

    CAS  PubMed  Google Scholar 

  88. Kao HY, Ordentlich P, Koyano-Nakagawa N et al (1998) A histone deacetylase corepressor complex regulates the Notch signal transduction pathway. Genes Dev 12:2269–2277

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Oswald F, Winkler M, Cao Y et al (2005) RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence Notch target genes. Mol Cell Biol 25:10379–10390

    CAS  PubMed Central  PubMed  Google Scholar 

  90. Dou S, Zeng X, Cortes P et al (1994) The recombination signal sequence-binding protein RBP-2 N functions as a transcriptional repressor. Mol Cell Biol 14:3310–3319

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Morel V, Schweisguth F (2000) Repression by suppressor of hairless and activation by Notch are required to define a single row of single-minded expressing cells in the Drosophila embryo. Genes Dev 14:377–388

    CAS  PubMed Central  PubMed  Google Scholar 

  92. Barolo S, Stone T, Bang AG et al (2002) Default repression and Notch signaling: hairless acts as an adaptor to recruit the corepressors Groucho and dCtBP to suppressor of hairless. Genes Dev 16:1964–1976

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Bray S, Furriols M (2001) Notch pathway: making sense of suppressor of hairless. Curr Biol 11:R217–R221

    CAS  PubMed  Google Scholar 

  94. Kurooka H, Honjo T (2000) Functional interaction between the mouse notch1 intracellular region and histone acetyltransferases PCAF and GCN5. J Biol Chem 275:17211–17220

    CAS  PubMed  Google Scholar 

  95. Wallberg AE, Pedersen K, Lendahl U et al (2002) p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitro. Mol Cell Biol 22:7812–7819

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Oswald F, Tauber B, Dobner T et al (2001) p300 acts as a transcriptional coactivator for mammalian Notch-1. Mol Cell Biol 21:7761–7774

    CAS  PubMed Central  PubMed  Google Scholar 

  97. Fryer CJ, Lamar E, Turbachova I et al (2002) Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex. Genes Dev 16:1397–1411

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Hubbard EJ, Wu G, Kitajewski J et al (1997) sel-10, a negative regulator of lin-12 activity in Caenorhabditis elegans, encodes a member of the CDC4 family of proteins. Genes Dev 11:3182–3193

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Oberg C, Li J, Pauley A et al (2001) The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog. J Biol Chem 276:35847–35853

    CAS  PubMed  Google Scholar 

  100. Wu G, Lyapina S, Das I et al (2001) SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation. Mol Cell Biol 21:7403–7415

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Gupta-Rossi N, Le Bail O, Gonen H et al (2001) Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor. J Biol Chem 276:34371–34378

    CAS  PubMed  Google Scholar 

  102. del Alamo D, Rouault H, Schweisguth F (2011) Mechanism and significance of cis-inhibition in Notch signalling. Curr Biol 21:R40–R47

    PubMed  Google Scholar 

  103. Becam I, Fiuza UM, Arias AM et al (2010) A role of receptor Notch in ligand cis-inhibition in Drosophila. Curr Biol 20:554–560

    CAS  PubMed  Google Scholar 

  104. Sprinzak D, Lakhanpal A, Lebon L et al (2011) Cis-interactions between Notch and Delta generate mutually exclusive signalling states. Nature 465:86–90

    Google Scholar 

  105. Yamamoto S, Charng WL, Rana NA et al (2012) A mutation in EGF repeat-8 of Notch discriminates between Serrate/Jagged and Delta family ligands. Science 338:1229–1232

    CAS  PubMed Central  PubMed  Google Scholar 

  106. Aster JC, Simms WB, Zavala-Ruiz Z et al (1999) The folding and structural integrity of the first LIN-12 module of human Notch1 are calcium-dependent. Biochemistry 38:4736–4742

    CAS  PubMed  Google Scholar 

  107. Rand MD, Grimm LM, Artavanis-Tsakonas S et al (2000) Calcium depletion dissociates and activates heterodimeric notch receptors. Mol Cell Biol 20:1825–1835

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Hori K, Sen A, Kirchhausen T et al (2012) Regulation of ligand-independent Notch signal through intracellular trafficking. Commun Integr Biol 5:374–376

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Fortini ME, Bilder D (2009) Endocytic regulation of Notch signaling. Curr Opin Genet Dev 19:323–328

    CAS  PubMed Central  PubMed  Google Scholar 

  110. Gordon WR, Vardar-Ulu D, Histen G et al (2007) Structural basis for autoinhibition of Notch. Nat Struct Mol Biol 14:295–300

    CAS  PubMed  Google Scholar 

  111. Gordon WR, Roy M, Vardar-Ulu D et al (2009) Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL. Blood 113:4381–4390

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Stankiewicz P, Lupski JR (2010) Structural variation in the human genome and its role in disease. Annu Rev Med 61:437–455

    CAS  PubMed  Google Scholar 

  113. Lupski JR, Belmont JW, Boerwinkle E et al (2013) Clan genomics and the complex architecture of human disease. Cell 147:32–43

    Google Scholar 

Download references

Acknowledgements

We apologize to our colleagues for not being able to cite their work given the length restrictions. S.Y. is a fellow of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital. H.J.B. is a Howard Hughes Medical Institute Investigator.

Author information

Authors and Affiliations

  1. Department of Molecular and Human Genetics, Program in Developmental Biology, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, 77030, USA

    Shinya Yamamoto

  2. Department of Molecular and Human Genetics and Howard Hughes Medical Institutes, Baylor College of Medicine, Houston, TX, 77030, USA

    Karen L. Schulze

  3. Department of Molecular and Human Genetics, Program in Developmental Biology, Department of Neuroscience, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, 77030, USA

    Hugo J. Bellen

Authors
  1. Shinya Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karen L. Schulze
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hugo J. Bellen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Shinya Yamamoto or Hugo J. Bellen .

Editor information

Editors and Affiliations

  1. Dept.of Molecular and Human Genetics, Program in Developmental Biology, Dept. of Neuroscience, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, USA

    Hugo J. Bellen

  2. Dept. of Molecular and Human Genetics, Program in Developmental Biology, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA

    Shinya Yamamoto

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Yamamoto, S., Schulze, K.L., Bellen, H.J. (2014). Introduction to Notch Signaling. In: Bellen, H., Yamamoto, S. (eds) Notch Signaling. Methods in Molecular Biology, vol 1187. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1139-4_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1139-4_1

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1138-7

  • Online ISBN: 978-1-4939-1139-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation