the functions of auxilin and rab11 in drosophila suggest that the fundamental role of ligand endocytosis in notch signaling cells is not recyclingauxilin的功能和rab11果蝇表明配体的基本角色等级信号细胞内吞作用不回收.pdfVIP

The Functions of Auxilin and Rab11 in Drosophila Suggest That the Fundamental Role of Ligand Endocytosis in Notch Signaling Cells Is Not Recycling Susan M. L. Banks1., Bomsoo Cho1., Suk Ho Eun1.¤, Ji-Hoon Lee1., Sarah L. Windler2., Xuanhua Xie1., 2 1 David Bilder , Janice A. Fischer * 1 Section of Molecular Cell and Developmental Biology and Institute for Cell and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America, 2 Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America Abstract Notch signaling requires ligand internalization by the signal sending cells. Two endocytic proteins, epsin and auxilin, are essential for ligand internalization and signaling. Epsin promotes clathrin-coated vesicle formation, and auxilin uncoats clathrin from newly internalized vesicles. Two hypotheses have been advanced to explain the requirement for ligand endocytosis. One idea is that after ligand/receptor binding, ligand endocytosis leads to receptor activation by pulling on the receptor, which either exposes a cleavage site on the extracellular domain, or dissociates two receptor subunits. Alternatively, ligand internalization prior to receptor binding, followed by trafficking through an endosomal pathway and recycling to the plasma membrane may enable ligand activation. Activation could mean ligand modification or ligand transcytosis to a membrane environment conducive to signaling. A key piece of evidence supporting the recycling model is the requirement in signaling cells for Rab11, which encodes a GTPase critical for endosomal recycling. Here, we use Drosophila Rab11 and auxilin mutants to test the ligand recycling hypothesis. First, we find that Rab11 is disp