title: Drosophila Crumbs prevents ectopic Notch activation in developing wings by inhibiting ligand-independent endocytosis.
abstract: Many signalling components are apically restricted in epithelial cells, and receptor localisation and abundance is key for morphogenesis and tissue homeostasis. Hence, controlling apicobasal epithelial polarity is crucial for proper signalling. Notch is a ubiquitously expressed, apically localised receptor, which performs a plethora of functions; therefore, its activity has to be tightly regulated. Here, we show that Drosophila Crumbs, an evolutionarily conserved polarity determinant, prevents Notch endocytosis in developing wings through direct interaction between the two proteins. Notch endocytosis in the absence of Crumbs results in the activation of the ligand-independent, Deltex-dependent Notch signalling pathway, and does not require the ligands Delta and Serrate or γ-secretase activity. This function of Crumbs is not due to general defects in apicobasal polarity, as localisation of other apical proteins is unaffected. Our data reveal a mechanism to explain how Crumbs directly controls localisation and trafficking of the potent Notch receptor, and adds yet another aspect of Crumbs regulation in Notch pathway activity. Furthermore, our data highlight a close link between the apical determinant Crumbs, receptor trafficking and tissue homeostasis.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, Dresden 01307, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Nemetschke
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, Dresden 01307, Germany knust@mpi-cbg.de.
authors.forename: Elisabeth
authors.identifier: 0000-0002-2732-9135
authors.initials: E
authors.lastname: Knust
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D016764:Cell Polarity / Q000502:physiology*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D034281:Dynamins / Q000037:antagonists & inhibitors / Q000235:genetics; D004705:Endocytosis / Q000502:physiology*; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000502:physiology; D005123:Eye / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D006835:Hydrazones / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014921:Wings, Animal / Q000196:embryology*
chemical_list: C086679:DX protein, Drosophila; D029721:Drosophila Proteins; D006835:Hydrazones; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497759:N protein, Drosophila; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D051880:Receptors, Notch; C000606278:Ser protein, Drosophila; C064360:crb protein, Drosophila; C064045:delta protein; D053829:Amyloid Precursor Protein Secretases; D034281:Dynamins
keywords: Crb–Notch interaction; Deltex; Ligand-independent Notch pathway; Wing vein refinement