Lipoprotein receptors and a disabled family cytoplasmic adaptor protein regulate EGL-17/FGF export in C. elegans.
Growth factors and morphogens need to be secreted to act on distant cells during development and in response to injury. Here, we report evidence that efficient export of a fibroblast growth factor (FGF), EGL-17, from the Caenorhabditis elegans developing vulva requires the lipoprotein receptor-related proteins Ce-LRP-1 and Ce-LRP-2 and a cytoplasmic adaptor protein, Ce-DAB-1 (Disabled). Lipoprotein receptors are transmembrane proteins best known for their roles in endocytosis. Ce-LRP-1 and Ce-LRP-2 possess a conserved intraluminal domain that can bind to EGL-17, as well as a cytosolic FXNPXY motif that can bind to Ce-DAB-1. Ce-DAB-1 contains signals that confer subcellular localization to Golgi-proximal vesicles. These results suggest a model in which Ce-DAB-1 coordinates selection of receptors and cargo, including EGL-17, for transport through the secretory pathway.
Kamikura
Darren M
DM
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Cooper
Jonathan A
JA
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D003593:Cytoplasm; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism* / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D006056:Golgi Apparatus; D049452:Green Fluorescent Proteins; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000378:metabolism; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism; D011233:Precipitin Tests; D018110:Receptors, Lipoprotein / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D013347:Subcellular Fractions; D020798:Two-Hybrid System Techniques; D014844:Vulva / Q000166:cytology / Q000254:growth & development*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; C478773:Dab2 protein, mouse; C105157:Egl-17 protein, C elegans; D036341:Intercellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D010750:Phosphoproteins; D018110:Receptors, Lipoprotein; D049452:Green Fluorescent Proteins; D005346:Fibroblast Growth Factors