Epsin potentiates Notch pathway activity in Drosophila and C. elegans.
Endocytosis and trafficking within the endocytosis pathway are known to modulate the activity of different signaling pathways. Epsins promote endocytosis and are postulated to target specific proteins for regulated endocytosis. Here, we present a functional link between the Notch pathway and epsins. We identify the Drosophila ortholog of epsin, liquid facets (lqf), as an inhibitor of cardioblast development in a genetic screen for mutants that affect heart development. We find that lqf inhibits cardioblast development and promotes the development of fusion-competent myoblasts, suggesting a model in which lqf acts on or in fusion-competent myoblasts to prevent their acquisition of the cardioblast fate. lqf and Notch exhibit essentially identical heart phenotypes, and lqf genetically interacts with the Notch pathway during multiple Notch-dependent events in Drosophila. We extended the link between the Notch pathway and epsin function to C. elegans, where the C. elegans lqf ortholog acts in the signaling cell to promote the glp-1/Notch pathway activity during germline development. Our results suggest that epsins play a specific, evolutionarily conserved role to promote Notch signaling during animal development and support the idea that they do so by targeting ligands of the Notch pathway for endocytosis.
Tian
Xiaolin
X
Department of Genetics, Washington University in St Louis, School of Medicine, 660 S. Euclid Avenue, St Louis, MO 63110, USA.
Hansen
Dave
D
Schedl
Tim
T
Skeath
James B
JB
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D017173:Caenorhabditis elegans; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D004705:Endocytosis; D019143:Evolution, Molecular; D018095:Germ-Line Mutation; D007150:Immunohistochemistry; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000166:cytology; D009154:Mutation; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D034622:RNA Interference; D051880:Receptors, Notch; D015398:Signal Transduction; D013045:Species Specificity; D019076:Transgenes; D033921:Vesicular Transport Proteins / Q000502:physiology*
D033942:Adaptor Proteins, Vesicular Transport; D029721:Drosophila Proteins; D008024:Ligands; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D033921:Vesicular Transport Proteins; C114154:epsin