Endocytic Trafficking of the Notch Receptor

  • Björn Schnute
  • Tobias Troost
  • Thomas KleinEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1066)


The endosomal pathway plays an important role in several aspects of Notch signalling ranging from ligand-dependent to independent activation and also degradation of the Notch receptor. Here, we will focus on its role during receptor degradation and describe the endosomal pathway with the components that are important for Notch degradation and the molecular machinery that orchestrates these events. Subsequently, we will describe the journey of Notch through the endosomal system and discuss the role of the genes involved. Mechanisms of the recently discovered ligand-independent activation of the Notch receptor in the endosomal pathway will be described and its contribution in physiologically Notch-dependent processes will be discussed. Last but not least, we will summarize the evidence for endosomal ligand-independent activation of the Notch pathway in vertebrates.


Notch Endocytosis Endosomal trafficking Endosome Lysosome ESCRT Ubiquitination Dx Su(dx) Lgd Shrub CHMP Endosomal maturation Degradation Recycling 



ATPase Associated with diverse cellular Activities


A Disintegrin and metalloprotease 10


Akt Kinase-Interacting Protein 1




Adaptor Protein


Cerebral Autosomal Dominant Artheriopathy with Subcortical Infarcts and Leukoencephalopathy


Casistas B-lineage lymphoma


Coiled-Coil and C2 domain-containing protein 1A


Coiled-Coil and C2 domain-containing protein 1B


Calcium-Caffeine-zinc sensititivity protein


Charged multivesicular body protein


COMM (Copper metabolism) domain containing protein 9


class C core vacuole/endosome tethering




CBF-1, Suppressor of Hairless, LAG-1




Delta-like 3


Drosophila melanogaster 14


Neural precursor cell expressed developmentally downregulated protein 4






Early Endosome


early endosomal antigene 2


Early Endosomal Vesicles


Epidermal growth factor


Endosomal sorting complex required for transport


Fibroblast growth factor


FRE under Dual Repression-Binding-Protein 1


FRE under Dual Repression-Binding-Protein 2




GTPase activating protein


GTPase dissociation factor


GDP-dissociation inhibitor


Guanosine diphosphate


Guanine nucleotide exchange factor


Green fluorescent protein




Guanosine triphosphate


homotypic fusion and protein sorting


Hepatocyte growth factor-regulated tyrosine kinase substrate


Heat shock cognate70


intracellular domain


intraluminal vesicle




Lysosome-associated membrane glycoprotein


Lethal giant discs


Lin-12 / Notch repeat


Maturing Endosome


Monensin sensitivity protein 1


Multivesicular body


Notch extracellular domain


Notch extracellular truncation


Notch intracellular domain


Negative Regulatory Region


Proline (P), Glutamic acid (E), Serine (S), Threonin(T)


Phosphatidylinositol 3,5-bisphoshphate


Phosphatidylinositol 3-phosphate


ras-related in brain


RBPJ-associated molecule


recombination signal binding protein for immunoglobulin kappa J region


Recycling Endosome


Receptor mediated Endocytosis 8






soluble N-ethylmaleimide-sensitive-factor attachment receptor


Sorting nexin


Signal transducing adaptor molecule


Suppressor of Deltex


Suppressor of Hairless


TBK1-associated Protein in Endolysosomes


Transmembrane proteins


tumor susceptibility gene 101




ubiquitin interacting motif


Vacoular protein sorting



Work in the Klein lab is supported by the Deutsche Forschungsgemeinschaft (DFG) through SFB 1208 “Identity and Dynamics of Membrane Systems-from Molecules to Cellular Functions “and Sachbeihilfe KL-1028/9-1 and KL-1028/8-1. We apologise to every researchers whose publications are not cited due to restrictions in space.


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of GeneticsHeinrich-Heine-UniversityDuesseldorfGermany

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