Endocytic regulation of notch signalling during development.
Delta/Notch signalling is of major importance for embryonic development and adult life. While endocytosis is often viewed as a way to down-regulate biological signals, ligand and receptor internalization are essential for Notch activation. The development of Drosophila mecanosensory bristles is a powerful model to study Delta/Notch signalling. Following the asymmetric division of bristle precursor cells, Delta ligands and Notch receptors traffic differently in the two daughter cells, leading to directional signal activation. Recent evidence suggests that in addition to differential ligand endocytosis after division, a subpopulation of multivesicular endosomes ensures the directional transport of Delta/Notch already during asymmetric cell division. Biochemical analysis suggests that different phases of endocytic Delta trafficking exert complementary but distinct actions required for ligand recycling, ligand/receptor interaction and ligand-mediated receptor activation, respectively. Finally, novel data suggest that different endosomal compartments may act as Delta/Notch signalling platforms. In this review, we discuss the implications of these novel findings for our cell biological understanding of Delta/Notch signalling.
Department of Biochemistry and Molecular Biology, University of Geneva, Sciences II, 30 quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland. Maximilian.Fuerthauer@unige.ch
Maximilian
M
Fürthauer
Marcos
M
González-Gaitán
D000818:Animals; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D051880:Receptors, Notch; C064045:delta protein