Lipoprotein receptors and a disabled family cytoplasmic adaptor protein regulate EGL-17/FGF export in C. elegans

Genes Dev. 2003 Nov 15;17(22):2798-811. doi: 10.1101/gad.1136103.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Amino Acid Motifs
  • Animals
  • Apoptosis Regulatory Proteins
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Movement
  • Cytoplasm
  • Female
  • Fibroblast Growth Factors / metabolism*
  • Fibroblast Growth Factors / pharmacology
  • Fluorescent Antibody Technique
  • Gene Silencing
  • Golgi Apparatus
  • Green Fluorescent Proteins
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Luminescent Proteins / metabolism
  • Mutation
  • Phosphoproteins / metabolism
  • Precipitin Tests
  • Receptors, Lipoprotein / metabolism*
  • Saccharomyces cerevisiae
  • Subcellular Fractions
  • Two-Hybrid System Techniques
  • Vulva / cytology
  • Vulva / growth & development*

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Apoptosis Regulatory Proteins
  • Caenorhabditis elegans Proteins
  • Dab2 protein, mouse
  • Egl-17 protein, C elegans
  • Intercellular Signaling Peptides and Proteins
  • Luminescent Proteins
  • Phosphoproteins
  • Receptors, Lipoprotein
  • Green Fluorescent Proteins
  • Fibroblast Growth Factors