Auxilin is essential for Delta signaling.
Endocytosis regulates Notch signaling in both signaling and receiving cells. A puzzling observation is that endocytosis of transmembrane ligand by the signaling cells is required for Notch activation in adjacent receiving cells. A key to understanding why signaling depends on ligand endocytosis lies in identifying and understanding the functions of crucial endocytic proteins. One such protein is Epsin, an endocytic factor first identified in vertebrate cells. Here, we show in Drosophila that Auxilin, an endocytic factor that regulates Clathrin dynamics, is also essential for Notch signaling. Auxilin, a co-factor for the ATPase Hsc70, brings Hsc70 to Clathrin cages. Hsc70/Auxilin functions in vesicle scission and also in uncoating Clathrin-coated vesicles. We find that like Epsin, Auxilin is required in Notch signaling cells for ligand internalization and signaling. Results of several experiments suggest that the crucial role of Auxilin in signaling is, at least in part, the generation of free Clathrin. We discuss these observations in the light of current models for the role of Epsin in ligand endocytosis and the role of ligand endocytosis in Notch signaling.
Eun
Suk Ho
SH
Section of Molecular Cell and Developmental Biology, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA.
Banks
Susan M L
SM
Fischer
Janice A
JA
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D034021:Auxilins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002966:Clathrin / Q000235:genetics / Q000378:metabolism; D033922:Clathrin Heavy Chains / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000254:growth & development / Q000378:metabolism; D017344:Genes, Insect; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D034021:Auxilins; D002966:Clathrin; D017931:DNA Primers; D029721:Drosophila Proteins; D050883:HSC70 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; C494336:Lqf protein, Drosophila; D008565:Membrane Proteins; C497759:N protein, Drosophila; D010446:Peptide Fragments; D051880:Receptors, Notch; D033921:Vesicular Transport Proteins; C559124:aux protein, Drosophila; C064045:delta protein; C114154:epsin; D033922:Clathrin Heavy Chains